Experimental Dermatology via MedWorm.com

Testosterone synthesized in cultured human SZ95 sebocytes derives mainly from dehydroepiandrosterone

Experimental Dermatology — Thu, 11 Mar 2010 00:00:00 +0100

Please cite this paper as: Testosterone synthesized in cultured human SZ95 sebocytes derives mainly from dehydroepiandrosterone. Experimental Dermatology 2010.Abstract: Human sebaceous gland possesses all the steroidogenic enzymes required for androgen synthesis. It remains unclear whether the testosterone produced in situ mainly derives from circulating dehydroepiandrosterone (DHEA) or from de novo synthesis utilizing serum cholesterol. Using testosterone radioimmunoassay, we found that testosterone was barely detectable in the supernatant of cultured human SZ95 sebocytes when cholesterol was added alone, indicating a low basal expression of steroidogenic acute regulatory protein (StAR) in SZ95 cells. Human chorionic gonadotropin and fibroblast growth factor-9 were as potent as forskolin ...

Akt inhibition up-regulates MMP1 through a CCN2-dependent pathway in human dermal fibroblasts

Experimental Dermatology — Fri, 26 Feb 2010 00:00:00 +0100

Please cite this article as: Akt inhibition up-regulates MMP1 through a CCN2-dependent pathway in human dermal fibroblasts. Experimental Dermatology 2010.Abstract: Akt is a key signalling molecule that was found to be down-regulated in chronic wounds. Akt blockade has dual antifibrotic effects in human dermal fibroblasts, by up-regulating matrix metalloproteinase 1 (MMP1) and down-regulating collagen gene expression (J Invest Dermatol 2008: 128: 1906). The aim of this study was to gain additional insights into the mechanism of MMP1 up-regulation following Akt blockade. As previous studies showed that CCN2 can be a positive regulator of MMP1, we examined the effects of Akt inhibition on CCN2 expression. Akt blockade using a specific pharmacological inhibitor and Akt siRNA resulted in a sign...

Reproducible pattern of microRNA in normal human skin

Experimental Dermatology — Thu, 25 Feb 2010 00:00:00 +0100

Please cite this paper as: Reproducible pattern of microRNA in normal human skin. Experimental Dermatology 2010.Abstract: MicroRNAs (miRNAs) regulate cell growth, differentiation and apoptosis via specific targeting of messenger RNA (mRNA). Aberrant mRNA expression contributes to pathological processes such as carcinogenesis. To take advantage of miRNA profiling in skin disease it is essential to investigate miRNA expression pattern in normal human skin. Here we investigated miRNA expression profiles from skin biopsies of 8 healthy volunteers taken from sun protected and mildly photo damaged skin using the modified protocol for miRNA extraction. We were able to show a constant pattern of miRNA expression between different individuals. We did not find any significant differences in miRNA ex...

Enzymes involved in the conversion of arachidonic acid to eicosanoids in the skin of atopic dogs

Experimental Dermatology — Thu, 25 Feb 2010 00:00:00 +0100

Please cite this paper as: Enzymes involved in the conversion of arachidonic acid to eicosanoids in the skin of atopic dogs. Experimental Dermatology 2010.Abstract: Canine atopic dermatitis (AD), a chronic inflammatory skin disease, shares characteristics with its human counterpart. To get insight into the role of enzymes involved in production of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), potent inflammatory mediators originating from membrane-derived arachidonic acid (AA), expression of genes encoding these enzymes and receptors was quantified by qPCR in non-lesional and lesional skin from atopic dogs and in healthy skin. Significantly higher mRNA expression of the key enzymes 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP), leukotriene A4 hydrolase (LTA4H) and prostaglandi...

Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub-clinical and clinical actinic keratosis during imiquimod treatment

Experimental Dermatology — Thu, 25 Feb 2010 00:00:00 +0100

Conclusion: The number of sub-clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using the CPL method. This is only a preliminary study with a small number of patients and as a result it is difficult to conclude both statistical and clinical significance. However, results were encouraging and indicate that larger studies are needed to demonstrate the relevance of these two new methods for improved detection of clinical and especially sub-clinical AK lesions. (Source: Experimental Dermatology)

The mouse frizzy (fr) and rat 'hairless' (frCR) mutations are natural variants of protease serine S1 family member 8 (Prss8)

Experimental Dermatology — Thu, 25 Feb 2010 00:00:00 +0100

Please cite this paper as: The mouse frizzy (fr) and rat 'hairless' (frCR) mutations are natural variants of protease serine S1 family member 8 (Prss8). Experimental Dermatology 2010.Abstract: We have previously suggested (based on genetic mapping analysis) that the allelic 'fuzzy' and 'hairless' mutations in the rat are likely orthologues of the mouse frizzy mutation (fr). Here, we analysed three large intraspecific backcross panels that segregated for mouse fr to restrict this locus to a 0.6-Mb region that includes fewer than 30 genes. DNA sequencing of one of these candidates known to be expressed in skin, protease serine S1 family member 8 (Prss8), revealed a T to A transversion associated with the fr allele that would result in a valine to aspartate substitution at residue 170 in the ...

Anti-inflammatory effects of the GABAB receptor agonist baclofen in allergic contact dermatitis

Experimental Dermatology — Thu, 25 Feb 2010 00:00:00 +0100

This study demonstrates a new role for the GABAB receptor in inflammation, making it a potential new therapeutic target to treat inflammatory skin diseases. (Source: Experimental Dermatology)

Confirmation of a disease model of pemphigus vulgaris: characterization and correlation between disease parameters in 90 mice

Experimental Dermatology — Thu, 25 Feb 2010 00:00:00 +0100

Please cite this paper as: Confirmation of a disease model of pemphigus vulgaris: characterization and correlation between disease parameters in 90 mice. Experimental Dermatology 2010.Abstract: Pemphigus vulgaris (PV) is a chronic autoimmune bullous disease associated with immunoglobulin G (IgG) autoantibodies against desmoglein 3 (Dsg3). Previously, a mouse model of PV was established by adoptive transfer of naive splenocytes from Dsg3[minus]/[minus] mice to Rag2[minus]/[minus] mice. The model is unique as Dsg3-specific naive lymphocytes from Dsg3[minus]/[minus] mice can be primed and activated by the endogenous Dsg3 in recipient mice, resulting in pathogenic anti-Dsg3 IgG without any active immunization. Here, we show that PV occurs after both intravenous (i.v.) and intraperitoneal (i.p....

Exploration of the functional hierarchy of the basal layer of human epidermis at the single-cell level using parallel clonal microcultures of keratinocytes

Experimental Dermatology — Thu, 25 Feb 2010 00:00:00 +0100

Please cite this paper as: Exploration of the functional hierarchy of the basal layer of human epidermis at the single-cell level using parallel clonal microcultures of keratinocytes. Experimental Dermatology 2010.Abstract: The basal layer of human epidermis contains both stem cells and keratinocyte progenitors. Because of this cellular heterogeneity, the development of methods suitable for investigations at a clonal level is dramatically needed. Here, we describe a new method that allows multi-parallel clonal cultures of basal keratinocytes. Immediately after extraction from tissue samples, cells are sorted by flow cytometry based on their high integrin-[alpha]6 expression and plated individually in microculture wells. This automated cell deposition process enables large-scale characteriz...

"Transcription physiology" of pigment formation in melanocytes: central role of MITF

Experimental Dermatology — Thu, 25 Feb 2010 00:00:00 +0100

Please cite this paper as:"Transcription physiology" of pigment formation in melanocytes: central role of microphthalmia-associated transcription factor (MITF). Experimental Dermatology 2010.Abstract: Melanin production is the primary mechanism protecting human skin against the UV light-induced damage. The polymeric compound melanin is synthesized within melanocytes in the specialized subcellular organelles, termed melanosomes, which are then transferred to surrounding keratinocytes. The genes for melanin synthesis and deposition are coordinately expressed in melanocytes. The transcription factor MITF, which has been reported to activate more than 25 genes in pigment cells, has emerged as an essential regulator not only for melanocyte development, proliferation and survival, but also for t...

Vitamin C attenuates ERK signalling to inhibit the regulation of collagen production by LL-37 in human dermal fibroblasts

Experimental Dermatology — Wed, 17 Feb 2010 00:00:00 +0100

This study shows that vitamin C enhances collagen production by inhibiting the ERK pathway induced by LL-37. (Source: Experimental Dermatology)

Association of UVRAG polymorphisms with susceptibility to non-segmental vitiligo in a Korean sample

Experimental Dermatology — Tue, 16 Feb 2010 00:00:00 +0100

This study suggests a possible association between UVRAG and NSV susceptibility. (Source: Experimental Dermatology)

Smoking but not homozygosity for CYP1A2 g-163A allelic variant leads to earlier disease onset in patients with sporadic porphyria cutanea tarda

Experimental Dermatology — Tue, 16 Feb 2010 00:00:00 +0100

In conclusion, this study provides evidence that smoking hastens the onset of cutaneous symptoms in sporadic-PCT patients. (Source: Experimental Dermatology)

Marie Unna hereditary hypotrichosis caused by a novel mutation in the human hairless transcript

Experimental Dermatology — Tue, 16 Feb 2010 00:00:00 +0100

Abstract: Recently the causes for various forms of hypotrichosis and atrichia have been identified, increasing our understanding of the pathways involved in hair cycling and morphogenesis. Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript were found as the cause for autosomal dominant Marie Unna hereditary hypotrichosis. At present, only two studies identified several pathogenic mutations. We ascertained a Jewish Ashkenazi family with hypotrichosis simplex of the Marie Unna type in a mother and her two children. Sequencing of the upstream ORF U2HR in the 5' UTR of the hairless gene resulted in the identification of a novel heterozygous missense mutation c.74C > T resulting in the amino acid change p.P25L. Functional assays confirmed that this mutatio...

HSP70 inducers from Chinese herbs and their effect on melanin production

Experimental Dermatology — Tue, 16 Feb 2010 00:00:00 +0100

In this study, we searched for HSP70 inducers from Chinese herbs and selected an ethanol extract of Eupatorium lindleyanum (E. lindleyanum). Not only melanin production but also the activity and expression of tyrosinase were significantly suppressed in cells treated with E. lindleyanum extract as well as in HSP70-overexpressing cells. The expression of MITF was clearly suppressed in cells treated with E. lindleyanum extract but not in HSP70-overexpressing cells. These results suggest that E. lindleyanum extract suppresses the expression of tyrosinase and melanin production through both HSP70-dependent and HSP70-independent mechanisms. (Source: Experimental Dermatology)

Skin wound healing in MMP2-deficient and MMP2 / Plasminogen double-deficient mice

Experimental Dermatology — Tue, 16 Feb 2010 00:00:00 +0100

Please cite this paper as: Skin wound healing in MMP2-deficient and MMP2/Plasminogen double-deficient mice. Experimental Dermatology.Abstract: During healing of incisional skin wounds, migrating keratinocytes dissect their way under the crust to re-epithelialize the wounded area. The efficiency of this tissue remodelling process depends on the concomitant activity of several extracellular proteases, including members of the plasminogen activation (PA) system and the matrix metalloproteinase (MMP) family. Treatment with the broad spectrum MMP inhibitor, galardin, delays wound healing in wildtype mice and completely arrest wound healing in plasminogen (Plg)-deficient mice, indicating a functional overlap between plasmin- and galardin-sensitive MMPs during wound healing. To address whether MM...

Increased levels of serum IL-31 in chronic spontaneous urticaria*

Experimental Dermatology — Tue, 16 Feb 2010 00:00:00 +0100

Please cite this paper as: Increased levels of serum IL-31 in chronic spontaneous urticaria. Experimental Dermatology 2010.Abstract: IL-31 represents a novel cytokine involved in pruritic skin diseases including atopic dermatitis (AD). We, therefore, aimed at investigating IL-31 levels in chronic spontaneous urticaria (CU). We included 46 patients with CU, 26 non-atopic skin healthy subjects as negative and 28 patients with AD as positive controls. IL-31 serum levels were analysed using commercial ELISA kit. IL-31 serum levels were higher in patients with CU compared to healthy controls (P < 0.001), but lower compared to patients with AD (P < 0.001). There was no difference in IL-31 serum levels in autologous serum skin test positive or negative CU patients and patients with infectious tri...

Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients

Experimental Dermatology — Tue, 16 Feb 2010 00:00:00 +0100

In conclusion, the use of the ectodomains of Dsg 3 and 1 as target antigens expressed in a human cell line resulted in sensitive and specific ELISA systems for both diagnosis and monitoring of PV and PF. (Source: Experimental Dermatology)

'Fish matters': the relevance of fish skin biology to investigative dermatology

Experimental Dermatology — Fri, 12 Feb 2010 00:00:00 +0100

Please cite this paper as:'Fish matters': The relevance of fish skin biology to investigative dermatology. Experimental Dermatology 2010.Abstract: Fish skin is a multi-purpose tissue that serves numerous vital functions including chemical and physical protection, sensory activity, behavioural purposes or hormone metabolism. Further, it is an important first-line defense system against pathogens, as fish are continuously exposed to multiple microbial challenges in their aquatic habitat. Fish skin excels in highly developed antimicrobial features, many of which have been preserved throughout evolution, and infection defense principles employed by piscine skin are still operative in human skin. This review argues that it is both rewarding and important for investigative dermatologists to revi...

Murine epidermal Langerhans cells and keratinocytes express functional P2X7 receptors

Experimental Dermatology — Mon, 25 Jan 2010 00:00:00 +0100

This study investigated whether murine epidermal cell subpopulations express functional purinergic P2X7 receptors. P2X7 expression was examined by immunoblotting and immunofluorescence staining of epidermal cells from C57Bl/6 mice. P2X7 function was evaluated by nucleotide-induced ethidium+ uptake measurements in epidermal cells from C57Bl/6 mice, and from P2X7 deficient mice and wild-type littermate controls. P2X7 was detected in whole epidermal cell preparations, and specifically on Langerhans cells (LCs) and keratinocytes (KCs). ATP induced ethidium+ uptake into LCs and KCs, with EC50 values of 503 and 482 [mu]m, respectively. BzATP, and to a lesser extent ATP[gamma]S and ADP, also induced ethidium+ uptake; while UTP, [alpha][beta]-meth-ATP and NAD were ineffective. ATP-induced ethidium...

Topical hydrocortisone, clobetasol propionate, and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice

Experimental Dermatology — Mon, 25 Jan 2010 00:00:00 +0100

Please cite this paper as: Topical hydrocortisone, clobetasol propionate, and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice. Experimental Dermatology 2010.Abstract: Topical corticosteroids such as hydrocortisone-17-butyrate (HCB) and clobetasol-17-propionate (CP) and vitamin D3 derivatives such as calcipotriol (CAL) are widely used to treat psoriasis. The immunosuppressive effects of corticosteroids make their topical use a concern for skin carcinogenicity. Few studies have assessed the effect of topical corticosteroids and topical vitamin D3 derivatives on photocarcinogenesis induced by ultraviolet radiation. We investigated whether HCB, CP, or CAL can accelerate photocarcinogenesis using simulated solar radiation (SSR). HCB, CP, ...

Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation

Experimental Dermatology — Mon, 25 Jan 2010 00:00:00 +0100

This study examined photoprotective effects of ellagic acid on collagen breakdown and inflammatory responses in UV (ultraviolet)-B irradiated human skin cells and hairless mice. Ellagic acid attenuated the UV-B-induced toxicity of HaCaT keratinocytes and human dermal fibroblasts. Non-toxic ellagic acid markedly prevented collagen degradation by blocking matrix metalloproteinase production in UV-B-exposed fibroblasts. Anti-wrinkle activity of ellagic acid was further investigated in hairless mice exposed to UV-B, in which it attenuated UV-B-triggered skin wrinkle formation and epidermal thickening. Topical application of 10 [mu]mol/l ellagic acid diminished production of pro-inflammatory cytokines IL-1[beta] and IL-6, and blocked infiltration of inflammatory macrophages in the integuments o...

N-acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen species

Experimental Dermatology — Mon, 25 Jan 2010 00:00:00 +0100

Please cite this paper as: N-acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen species. Experimental Dermatology 2010.Background: Chromium hypersensitivity is an important issue in occupational skin disease. When hexavalent chromium enters the cell, it can be reduced to trivalent chromium, resulting in the formation of reactive oxygen species (ROS). ROS are considered to play an important role in the progression of allergic contact dermatitis. N-acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant.Aims: We attempted to demonstrate that NAC could inhibit chromium hypersensitivity in a coadjuvant chromium-sensitized albino guinea pig model by counteractin...

Is there a 'gut–brain–skin axis'?

Experimental Dermatology — Mon, 25 Jan 2010 00:00:00 +0100

In conclusion, we are introducing a hypothesis, encouraged by our pilot observations and resting upon published prior evidence from the literature, which amalgamates previously proposed partial concepts into a new, unifying model, i.e. the gut[ndash]brain[ndash]skin axis. This concept suggests that modulation of the microbiome by deployment of probiotics can not only greatly reduce stress-induced neurogenic skin inflammation but even affect a very complex cutaneous phenomenon of (mini-) organ transformation, i.e. hair follicle cycling. These observations raise the intriguing prospect that feeding of just the right kind of bacteria can exert profound beneficial effects on skin homoeostasis, skin inflammation, hair growth and peripheral tissue responses to perceived stress. (Source: Experime...

Para-phenylenediamine-specific lymphocyte activation test: a sensitive in vitro assay to detect para-phenylenediamine sensitization in patients with severe allergic reactions

Experimental Dermatology — Mon, 25 Jan 2010 00:00:00 +0100

We examined nine patients with severe allergic reactions in response to permanent hair dyes. Patch tests using the standard concentration of 1% or 0.5% PPD resulted in severe and sometimes even bullous reactions in all patients responsive to PPD. Titration revealed that at 1% of the standard concentration (0.01% PPD), patch test sensitivity decreased and only 50% of patients responded. Consequently, we established an in vitro assay to diagnose PPD allergy. Freshly isolated peripheral blood mononuclear cells (PBMC) were cultured with titrated concentrations of PPD with or without IL-2 supplementation, and cell proliferation was determined by [3H]-thymidine incorporation. Lymphocyte activation test (LAT) detected PBMC cell proliferation specific to PPD, with at least 3.5-fold increase in [3H...

Alopecia in IL-10-deficient mouse pups is c-kit-dependent and can be triggered by iron deficiency

Experimental Dermatology — Sat, 23 Jan 2010 00:00:00 +0100

Please cite this paper as: Alopecia in IL-10-deficient mouse pups is c-kit-dependent and can be triggered by iron deficiency. Experimental Dermatology 2010.Abstract: Hair loss (alopecia) can result from a variety of metabolic, endocrine, immunologic, and environmental causes. This investigation was undertaken to determine the mechanisms underlying the sporadic development of alopecia in litters from C57BL/6 interleukin-10-deficient (Il10[minus]/[minus]) mice. All pups in affected litters demonstrated alopecia by postnatal days 17[ndash]19, with hair loss from their trunks but not from their head, base of tail, or feet. Histopathology revealed distorted hair follicles containing broken hair shafts and prominent dermal infiltrates containing increased numbers of activated mast cells. Hair re...

Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo

Experimental Dermatology — Fri, 22 Jan 2010 00:00:00 +0100

Please cite this paper as: Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo. Experimental Dermatology 2010.Abstract: Malignant melanoma (MM) is characterized by aggressive metastasis and high mortality rate. Microtubule-associated proteins 2 (MAP2) is expressed abundantly in majority of melanocytic nevi and primary melanomas, but absent in metastatic melanomas. To determine whether MAP2 correlates with tumor progression of MM, we investigated the effects of MAP2 inhibition on the biological behaviour of metastatic melanoma in vitro and in vivo. Our results demonstrated that adenovirus-mediated MAP2 induced apoptotic cell death and cell cycle arrest in metastatic human and mouse melanoma cell lines in vitro, and substantially ...

Atopic eczema or atopiform dermatitis

Experimental Dermatology — Fri, 22 Jan 2010 00:00:00 +0100

Please cite this paper as: Atopic eczema or atopiform dermatitis. Experimental Dermatology 2010.Abstract: Age period prevalence of atopic eczema (AE), a very common skin disease, has increased during the past decennia. This expansion seems to be ending in wealthy countries, while an increase is observed in developing nations, for which there is no firm explanation. Recent steps in understanding AE are the detection of skin barrier related filaggrin null mutations in approximately 25% of patients and the recognition of IL-31 as a molecule possibly involved in the itch (pruritus). Also interesting are the recognition of thymus and activation-regulated chemokine (TARC) and proliferating-inducing ligand (APRIL), as being associated with AE severity and activity. Immunocentric and corneocentric...

Heparanase activation induces epidermal hyperplasia, angiogenesis, lymphangiogenesis and wrinkles

Experimental Dermatology — Fri, 22 Jan 2010 00:00:00 +0100

Please cite this paper as: Heparanase activation induces epidermal hyperplasia, angiogenesis, lymphangiogenesis and wrinkles. Experimental Dermatology 2010.Abstract: To clarify the difference between cutaneous responses to single and repeated barrier disruption, changes of epidermal gene expression were examined by using RT-PCR. In repeatedly barrier-disrupted skin, heparanase was specifically up-regulated in epidermis. In addition, there was a marked decrease in heparan sulfate (HS) chains of perlecan in basement membrane at the dermal[ndash]epidermal junction (DEJ) compared with singly disrupted skin. HS chains form a reservoir for heparan sulfate-binding growth factors. In repeatedly barrier-disrupted skin, expression of vascular endothelial growth factor-A (VEGF-A), an angiogenic facto...

NF-κB is involved in inhibition of lipoxin A4 on dermal inflammation and hyperplasia induced by mezerein

Experimental Dermatology — Fri, 22 Jan 2010 00:00:00 +0100

Please cite this paper as: NF-[kappa]B is involved in inhibition of lipoxin A4 on dermal inflammation and hyperplasia induced by mezerein. Experimental Dermatology 2010.Abstract: The mechanisms by which lipoxin A4 (LXA4) inhibit skin inflammation remain unclear. In the present studies, the ear inflammatory model was induced by topical application of mezerein. Treatment of the mouse ear with LXA4 exhibited the inhibitory effects on oedema, neutrophil infiltration, vascular permeability, expressions of interleukin (IL)-1, IL-6 and IL-8 mRNA, DNA-binding activity of nuclear factor-[kappa]B (NF-[kappa]B), and on dermal hyperplasia. NF-[kappa]B reporter activities and nuclear translocations of NF-[kappa]B p65 in cultured keratinocytes stimulated by mezerein were inhibited by pretreatment of the...

Photodynamic therapy with topical methyl- and hexylaminolevulinate for prophylaxis and treatment of UV-induced SCC in hairless mice

Experimental Dermatology — Thu, 21 Jan 2010 00:00:00 +0100

Conclusions: PDT with HAL (2%, 6% and 20%) and MAL (20%) is equally effective to prevent and treat UV-induced SCC in hairless mice. (Source: Experimental Dermatology)

An improved, standardised protocol for the isolation, enrichment and targeted neural differentiation of Nestin+ progenitors from adult human dermis

Experimental Dermatology — Thu, 21 Jan 2010 00:00:00 +0100

Please cite this paper as: An improved, standardised protocol for the isolation, enrichment and targeted neural differentiation of Nestin+ progenitors from adult human dermis. Experimental Dermatology 2010.Abstract: Human skin-derived Nestin+ cells serve as a convenient source for autologous, adult, pluripotent progenitor cells that offer new therapeutic possibilities in cell-based regenerative medicine. However, the isolation of human Nestin+ cells has tended to be of very low efficiency and to produce highly variable cell yields. Here we report a standardised protocol that facilitates the isolation and enrichment of Nestin+ progenitor cells from enzymatically digested adult human scalp dermis. The use of distinct media like Dulbecco's modified Eagle medium supplemented with foetal bovine...

Modulating T cell functions does not alleviate chronic inflammatory skin lesions in K5.TGFβ1 transgenic mice

Experimental Dermatology — Wed, 20 Jan 2010 00:00:00 +0100

Please cite this paper as: Modulating T cell functions does not alleviate chronic inflammatory skin lesions in K5.TGF[beta]1 transgenic mice. Experimental Dermatology 2009.Abstract: To use mice with chronic hyperproliferative skin inflammation as psoriasis models, their thorough phenotypic and functional characterization is indispensable. Mice with keratin 5 promoter-controlled overexpression of latent human Transforming Growth Factor (TGF)[beta]1 within the basal epidermis (K5.TGF[beta]1 mice) show a psoriasiform phenotype, but the underlying pathogenic mechanisms are not entirely clear. To elucidate the contribution of T lymphocytes to the pathogenesis in K5.TGF[beta]1 mice, we used three complementary approaches: first, peripheral T cells were eradicated via systemic treatment with CD3-...

Enhanced MCP-1 release by keloid CD14+ cells augments fibroblast proliferation: role of MCP-1 and Akt pathway in keloids

Experimental Dermatology — Tue, 19 Jan 2010 00:00:00 +0100

Please cite this paper as: Enhanced MCP-1 release by keloid CD14+ cells augments fibroblast proliferation: role of MCP-1 and Akt pathway in keloids. Experimental Dermatology 2009.Abstract: Keloids are fibrous overgrowth induced by cutaneous injury. The pathogenesis of keloids is poorly understood, and no convincing animal model exists. Current hypotheses of the pathogenesis classify keloids as an entity of aberrant fibrosis. Hyperactivation of the MCP-1/CCR2 axis reportedly causes fibrosis in liver cirrhosis, atherosclerosis and lung fibrosis. Circulating CD14+ monocytes are precursors of circulating fibrocytes and contribute to fibrogenesis by a MCP-1/CCR2-dependent loop. As there is an increase in monocyte lineages in keloids, the aim of this study is to determine whether peripheral CD14...

Chemokine expression by human keratinocyte cell lines after activation of Toll-like receptors

Experimental Dermatology — Tue, 19 Jan 2010 00:00:00 +0100

This study aimed to determine if keratinocyte cell lines can be used for studies of innate immune mechanisms. Human primary keratinocytes and the HaCaT, CCD 1106 KERTr (KERTr) and HEK001 cell lines were treated with a panel of Toll-like receptor (TLR)-ligands. Expression of IL-8, CCL20, CXCL9 and CXCL10 was determined. All three cell lines expressed TLR1-6 and TLR9. KERTr cells responded to the same TLR-ligands as primary keratinocytes. Overall HEK001 responded similarly, but appeared to be relatively more sensitive to flagellin. This was in agreement with increased expression of TLR5. The expression profiles were most distinct in HaCaT cells. Furthermore, our data confirm and extend previously reported TLR7 and TLR8 independent IL-8 secretion by keratinocytes after Imiquimod treatment. Th...

Differential expression of antimicrobial peptides in margins of chronic wounds

Experimental Dermatology — Tue, 19 Jan 2010 00:00:00 +0100

Please cite this paper as: Differential expression of antimicrobial peptides in margins of chronic wounds. Experimental Dermatology 2009Abstract: Skin wounds usually heal without major infections, although the loss of the mechanical epithelial barrier exposes the tissue to various bacteria. One reason may be the expression of antimicrobial peptides (AMP) of which some [human [beta]-defensins (hBD) and LL-37] were recently shown to support additionally certain steps of wound healing. There are no studies which have compared expression patterns of different classes of AMP in chronic wounds. The aim of our study was therefore to analyse the expression profile of hBD-2, hBD-3, LL-37, psoriasin and RNase 7 by immunohistochemistry from defined wound margins of chronic venous ulcers. We detected ...

The role of ultraviolet radiation in melanomagenesis

Experimental Dermatology — Fri, 08 Jan 2010 00:00:00 +0100

Please cite this paper as: The role of ultraviolet radiation in melanomagenesis. Experimental Dermatology 2009Abstract: The role of ultraviolet radiation (UV) in the pathogenesis has been discussed controversially for many decades. Studies in mice (SCID, HGF/SF, SV40T) which develop malignant melanoma, show a role of UVB in melanomagenesis. In contrast to this, the role of UVA is less clear. We will review the recent in vitro and in vivo data in support of the hypothesis that UVA is also involved in the development of malignant melanoma. The role of UVA in p53 activation, apoptosis, cell cycle arrest and photoproduct formation is discussed. (Source: Experimental Dermatology)

Functional characterization of T cells differentiated in vitro from bone marrow-derived CD34+ cells of psoriatic patients with family history

Experimental Dermatology — Tue, 08 Dec 2009 00:00:00 +0100

Conclusions: T cells differentiated from CD34+ cells of psoriatic patients, but not normal controls, are functionally similar to psoriatic circulating T cells, suggesting that the dysfunctional activity of T cells in psoriatic patients can be traced back to the early development of haematopoietic cells. (Source: Experimental Dermatology)

Overexpression of connexin26 in the basal keratinocytes reduces sensitivity to tumor promoter TPA

Experimental Dermatology — Mon, 07 Dec 2009 00:00:00 +0100

Please cite this paper as: Overexpression of connexin26 in the basal keratinocytes reduces sensitivity to tumor promoter TPA. Experimental Dermatology 2009.Abstract: Connexin 26 is important in keratinocyte proliferation, differentiation and skin pathologies. Cx26 is barely expressed in normal adult epidermis, but its expression is induced during wound healing, psoriasis, and skin hyperplasia stimulated by tumor promoters. In hyperplastic proliferating epidermis, Cx26 is co-expressed with Cx43 typical for basal and suprabasal keratinocytes. As Cx26 and Cx43 can not form permeable gap junctions, their co-expression may alter the gap junctional communication between keratinocytes and induce proliferation. To test the effect of persistent co-expression of Cx26 and Cx43 in epidermis, we genera...

Whole genome transcriptional profiling identifies novel differentiation regulated genes in keratinocytes

Experimental Dermatology — Thu, 03 Dec 2009 00:00:00 +0100

Please cite this paper as: Whole genome transcriptional profiling identifies novel differentiation regulated genes in keratinocytes. Experimental Dermatology 2009.Abstract: Keratinocyte differentiation plays a pivotal role in the epidermal barrier. Single keratinocyte differentiation genes have already been studied, but many important constituents of this process may have been missed so far. Gene expression profiling by microarray was carried out in cultured normal human epidermal keratinocytes undergoing confluence-induced differentiation to find novel differentiation genes. Candidate gene lists were established and genes of potential dermatological interest were validated by quantitative reverse transcription polymerase chain reaction and immunohistochemical analysis. Some of these point...

Effects of metals on skin permeability barrier recovery

Experimental Dermatology — Tue, 01 Dec 2009 00:00:00 +0100

Please cite this paper as: Effects of metals on skin permeability barrier recovery. Experimental Dermatology 2009.Abstract: We previously demonstrated that the electrical state of the skin surface influences epidermal permeability barrier homeostasis. At the interface between different materials, electrons are localized heterogeneously and induce electrical potential. In the present study, we evaluated the effects of metals on the barrier recovery. When we put pure gold plate on skin immediately after tape stripping, the barrier recovery rate was faster than the control. The acceleration of barrier recovery was blocked when the plate was earthed (grounded). When a plastic membrane was sandwiched between the plate and the skin, the recovery was delayed in comparison with the control. We the...

Activating transcription factor 3 (ATF3) expression is increased in erythema multiforme and is regulated by IFN-γ in human keratinocytes

Experimental Dermatology — Mon, 30 Nov 2009 00:00:00 +0100

Please cite this paper as: Activating transcription factor 3 (ATF3) expression is increased in erythema multiforme and is regulated by IFN-[gamma] in human keratinocytes. Experimental Dermatology 2009.Abstract: Activating transcription factor 3 (ATF3) is a member of the ATF/cyclic AMP responsive element-binding protein (CREB) family of transcription factors and is involved in the regulation of immune responses, apoptosis, DNA repair and oncogenesis. The epidermal expression of ATF3 in the setting of cutaneous inflammation has not been well characterized. To examine the expression of ATF3 in the setting of inflammatory skin disease, ATF3 protein expression was analysed by immunohistochemistry (IHC). We found diffuse epidermal ATF3 protein expression in skin biopsies of erythema multiforme (...

Alternate trafficking of cathepsin L in dermal fibroblasts induced by UVA radiation

Experimental Dermatology — Mon, 30 Nov 2009 00:00:00 +0100

Please cite this paper as: Alternate trafficking of cathepsin L in dermal fibroblasts induced by UVA radiation. Experimental Dermatology 2009.Abstract: UVA radiation is increasingly used to treat fibrotic skin disorders. However, the mechanisms underlying the therapeutic effects of UVA for these disorders are only partially understood. Cathepsin L is a lysosomal cysteine protease, which has been shown to degrade various matrix proteins thus contributing to extracellular remodeling. Therefore, we investigated whether UVA irradiation regulates the expression and release of cathepsin L in human dermal fibroblasts. No alterations were found after single irradiation; however, a significantly increased extracellular release of cathepsin L was observed after repeated irradiation up to four times....

Decreased expression of neurofibromin contributes to epithelial–mesenchymal transition in neurofibromatosis type 1

Experimental Dermatology — Mon, 30 Nov 2009 00:00:00 +0100

Please cite this paper as: Decreased expression of neurofibromin contributes to epithelial[ndash]mesenchymal transition in neurofibromatosis type 1. Experimental Dermatology 2009.Abstract: Plexiform and/or dermal neurofibromas are nerve sheath tumors of the peripheral nervous system that are usually present in individuals with neurofibromatosis type 1 (NF1). Neurofibromas arise from Schwann cells with biallelic inactivation of NF1, the gene that encodes neurofibromin. This protein is responsible for regulation of the Ras-mediated pathway, which has been shown to play a crucial role in epithelial-to-mesenchymal transition (EMT). EMT is a biological process that occurs during embryogenesis and wound healing and is involved in pathological processes such as organ fibrosis and cancer metastasi...

A simple assay for the study of human hair follicle damage induced by ionizing irradiation

Experimental Dermatology — Thu, 19 Nov 2009 00:00:00 +0100

Please cite this paper as: A simple assay for the study of human hair follicle damage induced by ionizing irradiation. Experimental Dermatology 2009.Abstract: Due to its rapidly proliferating matrix keratinocytes, the hair follicle is highly sensitive to ionizing irradiation (IR)-induced skin damage and thus an instructive and clinically relevant model organ for investigating the effects of IR on rapidly dividing epithelial-mesenchymal interaction systems. Here, we have assessed the impact of IR on organ-cultured human scalp hair follicles. We show that IR significantly inhibits the proliferation and induces apoptosis of hair follicle matrix keratinocytes, disrupts normal hair follicle pigmentation, and upregulates a number of quantitative toxicity and viability markers (oxidative stress i...

The mineralocorticoid receptor as a novel player in skin biology: beyond the renal horizon?

Experimental Dermatology — Wed, 18 Nov 2009 00:00:00 +0100

Please cite this paper as: The mineralocorticoid receptor as a novel player in skin biology: beyond the renal horizon? Experimental Dermatology 2009.Abstract: The mineralocorticoid receptor (MR) and its ligand aldosterone regulate renal sodium reabsorption and blood pressure and much knowledge has been accumulated in MR physiopathology, cellular and molecular targets. In contrast, our understanding of this hormonal system in non-classical targets (heart, blood vessels, neurons, keratinocytes[hellip]) is limited, particularly in the mammalian skin. We review here the few available data that point on MR in the skin and that document cutaneous MR expression and function, based on mouse models and very limited observations in humans. Mice that overexpress the MR in the basal epidermal keratino...

Can blood components with age-related changes influence the ageing of endothelial cells?

Experimental Dermatology — Wed, 18 Nov 2009 00:00:00 +0100

In conclusion, our data suggest that blood components that exhibit age-related changes, such as alterations in cytoskeletal regulators and stress proteins, may be associated with endothelial cell ageing. (Source: Experimental Dermatology)

In vivo synthesis and secretion of erythropoietin by genetically modified primary human keratinocytes grafted onto immunocompromised mice

Experimental Dermatology — Tue, 03 Nov 2009 00:00:00 +0100

Conclusion: Keratinocytes carry the potential to serve as a genetically modified biofactory synthesizing human EPO. In vivo gene selection does not allow to select for increased EPO secretion, most likely because of altered secretory activity of transduced KC in the stratified, differentiated epidermis. Thus, further studies are necessary to optimize the release of EPO by genetically modified KC. (Source: Experimental Dermatology)

CD40 signalling induces IL-10-producing, tolerogenic dendritic cells

Experimental Dermatology — Mon, 02 Nov 2009 00:00:00 +0100

This study was designed to characterize the role of the CD40-CD40L pathway for differentiation and function of human DC. Therefore, iDC were stimulated through CD40-CD40L interaction by transduction of DC with adenoviral vectors encoding for CD40L (Ad-CD40L). Resulting DC (CD40L-DC) were analysed concerning their phenotype, cytokine profile and T cell stimulatory capacity. Transduction induced a DC phenotype comparable to stimulation with proinflammatory cytokines as revealed by upregulation of CD83 and the costimulatory molecules CD80 and CD86. Additionally, Ad-CD40L-induced strong production of IL-12p70 not observed in cytokine-matured DC. Surprisingly, the T cell stimulatory capacity was markedly reduced in CD40L-DC. Furthermore, stimulation of CD8+ T cells by peptide-loaded CD40L-DC re...

Reflectance confocal microscopy for pigmentary disorders

Experimental Dermatology — Mon, 02 Nov 2009 00:00:00 +0100

This article reviewed the RCM applications in the characterization and management of pigmentary disorders. The application of RCM in pigmentary disorders has been expanded to describe hyper- and hypopigmentary disorders as well as pigmented skin tumors. The great advantages of non-invasive and repetitive examination of RCM may provide its usefulness not only in the diagnosis and management of pigmentary disorders, but also in researching pathogenesis of pigmentary disorders. (Source: Experimental Dermatology)

Increased alpha-melanocyte-stimulating hormone (α-MSH) levels and melanocortin receptors expression associated with pigmentation in an NC/Nga mouse model of atopic dermatitis

Experimental Dermatology — Mon, 02 Nov 2009 00:00:00 +0100

Please cite this paper as: Increased alpha-melanocyte-stimulating hormone ([alpha]-MSH) levels and melanocortin receptors expression associated with pigmentation in an NC/Nga mouse model of atopic dermatitis. Experimental Dermatology 2009.Abstract: Patients with a specific subtype of atopic dermatitis (AD) display particular patterns of pigmentation, such as ripple pattern pigmentation on the neck, pigmented macules on the lip and diffuse pigmentation. However, the mechanism underlying these patterns has not been determined. The purpose of our research is to investigate the factors influencing this type of pigmentation in AD. We observed that AD model mice (NC/Nga mice) displayed an increase in the number of 3, 4-dihydroxyphenylalanine (Dopa)-positive melanocytes in the epidermis and intes...

Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation

Experimental Dermatology — Mon, 02 Nov 2009 00:00:00 +0100

In this study, skin biopsies from both healthy-looking and lesional skin of patients with psoriasis and superficial spreading BCC were collected and the expression of PAR-2 immunoreactivity in tryptase-positive mast cells was analysed. PAR-2 expression was confirmed in vitro in different mast cell populations. Cord-blood derived mast cells (CBMC) were stimulated with a PAR-2 activating peptide, 2-furoyl-LIGRLO-NH2. Consequently, IL-8 and histamine production was analysed in the supernatants. We observed a significant increase in the percentage of mast cells expressing PAR-2 in the lesional skin of psoriasis and BCC patients compared with the healthy-looking skin. HMC-1.2, LAD-2 and CBMC mast cells all expressed PAR-2 both intracellularly and on the cell surface. CBMC activation with the PA...

Topical treatment with the vitamin D analogue calcipotriol enhances the upregulation of the antimicrobial protein hCAP18/LL-37 during wounding in human skin in vivo

Experimental Dermatology — Thu, 29 Oct 2009 00:00:00 +0100

Please cite this paper as: Topical treatment with the vitamin D analogue calcipotriol enhances the upregulation of the antimicrobial protein hCAP18/LL-37 during wounding in human skin in vivo. Experimental Dermatology 2009.Abstract: Cathelicidin antimicrobial protein, hCAP18, is the sole cathelin protein in human. Its C-terminal peptide, which is released enzymatically from the holoprotein, has broad antimicrobial activity but also has effects on eukaryotic cells. hCAP18 is present in leukocytes and is produced at epithelial interfaces as part of the innate immune system. In normal intact skin, there is low constitutive expression of hCAP18, which is rapidly upregulated upon injury. Accumulating evidence indicates that hCAP18/LL-37 may serve a key role in protecting the integrity of the ep...

Effect of topical application and intraperitoneal injection of oregonin on atopic dermatitis in NC/Nga mice

Experimental Dermatology — Wed, 21 Oct 2009 23:00:00 +0100

Please cite this paper as: Effect of topical application and intraperitoneal injection of oregonin on atopic dermatitis in NC/Nga mice. Experimental Dermatology 2009.Abstract: The diarylheptanoid, oregonin (ORE), which was isolated from the bark of Alnus japonica Steudel that grows natively in Korea, has been known to exert antioxidative, anti-inflammatory, anti-cancer and immune response inhibitory effects. The antioxidative effect of ORE was observed on the superoxide and 1,1-diphenyl-2-picrylhydrazyl radical, as well as on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated RAW264.7 macrophages. The statistically significant inhibitory action of ORE against production of cytokines induced by bacterial products or by interleukin (IL)-1[bet...

Mouse models for melanoma: a personal perspective

Experimental Dermatology — Wed, 21 Oct 2009 23:00:00 +0100

Please cite this paper as: Mouse models for melanoma: a personal perspective. Experimental Dermatology 2009.Abstract: Complex biological processes often require in vivo analysis, and many important research advances have been made using mice as a model for the study of various biological systems. Cutaneous melanomas are tumors originating from skin melanocytes, which are present in hair follicles, and interfollicular epidermal and dermal layers. Until recently, mouse melanoma models were largely based on transplantation models, i.e. transplantation of either syngeneic or xenogeneic melanoma cells into wild type or genetically modified animals. More recently, however, the use of novel technologies specifically modifying the genome allows for the generation of mouse strains, which may develo...

Influence of narrowband UVB phototherapy on vitamin D and folate status

Experimental Dermatology — Wed, 21 Oct 2009 23:00:00 +0100

Conclusion: Low-dose nUVB treatment gives a significant increase (P < 0.001) of the vitamin D status in persons with low initial levels of 25(OH)D, but no effect on the folate level. (Source: Experimental Dermatology)

Dysregulation of CD36 upon TLR-2 stimulation in monocytes from patients with atopic dermatitis and the TLR2 R753Q polymorphism

Experimental Dermatology — Wed, 21 Oct 2009 23:00:00 +0100

Conclusion: The differences in CD36 expression in TLR-2 polymorph AD patients compared to wild type AD patients and healthy controls may be associated with an enhanced susceptibility to skin infections with S. aureus. (Source: Experimental Dermatology)

Upregulation of cathepsin S in psoriatic keratinocytes

Experimental Dermatology — Wed, 21 Oct 2009 23:00:00 +0100

Please cite this paper as: Upregulation of cathepsin S in psoriatic keratinocytes. Experimental Dermatology 2009.Abstract: Cathepsin S (CATS) is a cysteine protease, well known for its role in MHC class II-mediated antigen presentation and extracellular matrix degradation. Disturbance of the expression or metabolism of this protease is a concomitant feature of several diseases. Given this importance we studied the localization and regulation of CATS expression in normal and pathological human/mouse skin. In normal human skin CATS-immunostaining is mainly present in the dermis and is localized in macrophages, Langerhans, T- and endothelial cells, but absent in keratinocytes. In all analyzed pathological skin biopsies, i.e. atopic dermatitis, actinic keratosis and psoriasis, CATS staining is...

Lipidome of narrow-band ultraviolet B irradiated keratinocytes shows apoptotic hallmarks

Experimental Dermatology — Tue, 20 Oct 2009 23:00:00 +0100

Conclusions: NB-UVB affected the cellular lipidome of keratinocytes in strictly apoptosis-specific manner. (Source: Experimental Dermatology)

Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin model

Experimental Dermatology — Tue, 20 Oct 2009 23:00:00 +0100

Please cite this paper as: Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin model. Experimental Dermatology 2009.Abstract: An ex vivo porcine skin model was utilized to analyse the penetration of 5-aminolevulinic acid (5-ALA) contained in a nanoemulsion-based formulation BF-200 ALA (10% 5-ALA-hydrochloride) versus 16% aminolevulinate methyl ester-hydrochloride in a commercially cream (MAL cream) by fluorescence microscopy of their common metabolite protoporphyrin IX (PpIX) after 3, 5, 8 and 12 h. Fluorescence signals of PpIX in pig skin treated with BF-200 ALA were stronger than those for MAL cream. At 8 and 12 h, the PpIX fluorescence signals were 4.8- and 5.0-fold higher than those measu...

Corrigendum

Experimental Dermatology — Tue, 20 Oct 2009 23:00:00 +0100

(Source: Experimental Dermatology)

The NF-κB signalling pathway is involved in the LPS/IL-2-induced upregulation of FoxP3 expression in human CD4+CD25high regulatory T cells

Experimental Dermatology — Tue, 20 Oct 2009 23:00:00 +0100

Please cite this paper as: The NF-[kappa]B signalling pathway is involved in the LPS/IL-2-induced upregulation of FoxP3 expression in human CD4+CD25high regulatory T cells. Experimental Dermatology 2009.Abstract: Regulatory T cells (Treg) have been found to be central for host defense regulation against microbial antigens, the prevention of allergic and autoimmune diseases and the suppression of effective tumor immune responses. However, the influence of the microenvironment and the mechanisms leading to their activation in the periphery still remain unclear. In vitro infection models revealed that survival and suppressive function of Treg is improved when they are confronted with lipopolysaccharide (LPS). Because LPS initiates signalling via the receptor Toll-like receptor 4 (TLR4) and th...

Nestin and SOX9 and SOX10 transcription factors are coexpressed in melanoma

Experimental Dermatology — Tue, 20 Oct 2009 23:00:00 +0100

In this study, the expression levels of nestin, BRN2, SOX9 and SOX10 were analysed in tissues of melanoma (n = 78) and melanocytic nevi (n = 26) by immunohistochemistry. All proteins were highly expressed in primary and metastatic melanomas and, apart from BRN2, showed much lower levels in melanocytic nevi. Significant coexpression of nestin with SOX9 and SOX10 was found in primary melanoma confirming our in vitro data. Correlation analysis with clinicopathological data revealed that nestin was significantly associated with presence of ulceration in primary tumors and SOX9 with more advanced stage of disease. Our data reveal that SOX9 and SOX10 are highly expressed in melanoma and seem to have a regulatory role in nestin expression. The association with ulceration and advanced-stage tumors...

Probing tumor and peritumoral tissues in superficial and nodular basal cell carcinoma using polarized Raman microspectroscopy

Experimental Dermatology — Tue, 20 Oct 2009 23:00:00 +0100

This study reports the use of polarized Raman microspectroscopy on the nodular and superficial types to discriminate between healthy epidermis and tumor, and between normal and peritumoral stroma. This technique probes additional information than conventional Raman spectroscopy because it is sensitive to the molecular ordering of tissue components. Depolarization ratios and hierarchical cluster analysis demonstrate that polarized Raman microspectroscopy can better identify the tumor and the peritumoral dermis than conventional Raman microspectroscopy, and hence gives potential complementary data about their molecular characteristics (molecular composition, secondary structure of proteins, intra- and/or inter-molecular bonding). Our findings also show that although superficial and nodular t...

Absence of modulation of CD4+CD25high regulatory T cells in CTCL patients treated with bexarotene

Experimental Dermatology — Tue, 20 Oct 2009 23:00:00 +0100

Please cite this paper as: Absence of modulation of CD4+CD25high regulatory T cells in CTCL patients treated with bexarotene. Experimental Dermatology 2009.Abstract: Cutaneous T-cell lymphoma (CTCL) are a heterogeneous group of lymphoproliferative disorders, characterized by the infiltration of the epidermis by mature and activated malignant CD4+ T-lymphocytes. Retinoids such as retinoic acid and synthetic analogues have long been used alone or in combination with other therapies for CTCL. Bexarotene, the first synthetic highly selective RXR retinoid, was approved for the treatment of all stages of CTCL in patients refractory to at least one systemic therapy. Recently, six cases in which the initiation of bexarotene therapy for CTCL was associated with the progression of internal disease d...

Effect of honey and its major royal jelly protein 1 on cytokine and MMP-9 mRNA transcripts in human keratinocytes

Experimental Dermatology — Tue, 20 Oct 2009 23:00:00 +0100

Please cite this paper as: Effect of honey and its major royal jelly protein 1 on cytokine and MMP-9 mRNA transcripts in human keratinocytes. Experimental Dermatology 2009: 00: 000[ndash]000.Abstract: Honey has been used since ancient times as a remedy in wound healing. However, even though the results from randomized clinical trials document that honey accelerates wound healing, no study dealing with its influence on human skin cells (epidermal keratinocytes and dermal fibroblast) has been performed. We demonstrate that keratinocytes, which are known to be involved in wound healing, are responsible for elevated production of mediators including cytokines (TNF-[alpha], IL-1[beta] and TGF-[beta]) and matrix metalloproteinase-9 (MMP-9) after incubation with honey. Real-time PCR was performed...

About the cutaneous targets of bexarotene in CTCL patients

Experimental Dermatology — Tue, 20 Oct 2009 23:00:00 +0100

Please cite this paper as: About the cutaneous targets of bexarotene in CTCL patients. Experimental Dermatology 2009.Abstract: There are several approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are one of the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. Bexarotene has been demonstrated to act on malignant T-cells by inducing their apoptosis, but nothing is known about its role on keratinocytes and Langerhans cells. Immunohistochemical analysis using CD1a, HLA-DR, ICAM-1 (activation markers), CD95 and CD40 (apoptosis markers) was conducted on frozen sections of bexarotene-exposed cutaneous explants and skin biopsy specimens from patients treated with bexarotene. None of the studied markers was significantly m...

The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines

Experimental Dermatology — Wed, 23 Sep 2009 23:00:00 +0100

Please cite this paper as: The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines. Experimental Dermatology 2009.Abstract: Solar lentigines (SLs) are hyperpigmentary lesions presented on sun-exposed areas of the skin and associated with ageing. The molecular mechanism of SL initiation is not completely understood. Ultraviolet B (UVB) stimulates keratinocytes to produce interlukin-1 alpha (IL-1[alpha]), which then induces keratinocyte growth factor (KGF) secretion; therefore, we examined their possible roles in the induction of SLs. We found that KGF increases pigment production in both pigmented epidermal equivalents and human skin explants. In addition, UVB exposure increases KGF expression, and KGF treatment induces tyrosinase...

Hirseins inhibit melanogenesis by regulating the gene expressions of Mitf and melanogenesis enzymes

Experimental Dermatology — Wed, 16 Sep 2009 23:00:00 +0100

We report for the first time that HA and HB can down-regulate melanogenesis by down-regulating Mitf gene expression, leading to reduced expressions of Tyr, Trp1 and Dct. The hirseins were also able to reduce the kinase activity, suggesting the possible involvement of PKC in the overall ability of the hirseins to down-regulate melanogenesis. (Source: Experimental Dermatology)

Large scale study of epidermal recovery after stratum corneum removal: dynamics of genomic response

Experimental Dermatology — Wed, 16 Sep 2009 23:00:00 +0100

Please cite this paper as: Large scale study of epidermal recovery after stratum corneum removal: dynamics of genomic response. Experimental Dermatology 2009.Abstract: The stratum corneum (SC) is a superficial skin compartment that protects the body from the outside environment. Any disturbance of this function induces cascading steps of molecular and cellular repair in the whole epidermis. The aim of this study was to investigate epidermal gene expression following SC removal by tape stripping. Twenty-nine healthy male volunteers were included (27 ± 4 years old). Tape stripping was processed on one inner forearm, the other unstripped forearm served as a control. Epidermis samples were collected at 2, 6, 19, 30 and 72 h after tape stripping. Trans-epidermal water loss measurements were pe...

Intracellular delivery of major histocompatibility complex class I-binding epitopes: dendritic cells loaded and matured with cationic peptide/poly(I:C) complexes efficiently activate T cells

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

Abstract: Based on their role for the induction of T-cell responses, dendritic cells (DCs) are popular candidates in cancer vaccine development. We established a novel single-step intracellular delivery of peptide/poly(I:C) complexes for antigen loading and Toll-like receptor-3 (TLR3)-mediated maturation of human DCs using a cell-penetrating peptide (tat49[ndash]57: RKKRRQRRR) as delivery vector. Towards this end, a cationic tat-sequence was fused with an antigenic, major histocompatibility complex (MHC) class I-binding melanoma epitope (Melan-A/Mart-1 sequence: ELAGIGILTV) and then mixed with negatively charged poly(I:C) dsRNA to form peptide/nucleic acid complexes. Flow cytometry and confocal laser scanning microscopy confirmed intracellular localization of TLR3 in monocyte-derived immat...

Topical calcitriol protects from UV-induced genetic damage but suppresses cutaneous immunity in humans

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

Abstract: Calcitriol, the biologically active form of vitamin D, has been reported to cause both suppressive and protective immune effects in mice. Its immune effects in vivo in humans are unclear. We investigated the in vivo effects of topical calcitriol on minimal erythema dose and skin immune responses in healthy volunteers. We found that calcitriol did not protect from ultraviolet (UV)-induced erythema (sunburn) when applied either 24 h before or immediately after irradiation, although it decreased the density of sunburn cells and thymine dimers seen on biopsy when applied 24 h before and again immediately after irradiation. Using the Mantoux reaction as a model of skin immunity, we found that topical calcitriol applied at high total doses reduced the Mantoux responses of nearby untrea...

Efficacy of quantifying melanosome transfer with flow cytometry in a human melanocyte–HaCaT keratinocyte co-culture system in vitro

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

In this study, we describe a simple, specific, reproducible and quantitative assay system to assess melanosome transfer. We first established a co-culture model of normal human epidermal melanocytes and HaCaT keratinocytes. The cells were co-cultured for 72 h in a serum-free keratinocyte growth media and double labelled with Fluorescein isothiocyanate (FITC)-conjugated antibody against the melanosome-specific protein gp100, and with Phycoerythrin (PE)-conjugated antibody against the keratinocyte-specific marker cytokeratin. Then, the cells were examined using co-focal microscope and flow cytometry. The increased melanosome transfer from melanocytes to HaCaT keratinocytes was observed in a time-dependent manner. To verify the accessibility of this method, two known melanosome transfer inhib...

Activation of toll-like receptors 2, 3 or 5 induces matrix metalloproteinase-1 and -9 expression with the involvement of MAPKs and NF-κB in human epidermal keratinocytes

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

In this study, we demonstrate that the mRNA and protein expressions of MMP-1 and MMP-9 in human epidermal keratinocytes are induced by ligands for TLR2, TLR3 and TLR5 [Pam3CSK4, Poly(I:C) and flagellin, respectively] in a dose-dependent manner. We also found that the ligands for TLR2, TLR3 and TLR5 activate the MAP kinases, JNK and p38 MAPK, but not ERK1/2. Furthermore, treatment with the ligands for TLR2, TLR3 and TLR5 also induced the degradation of I[kappa]B-[alpha] and activated the nuclear translocation of NF-[kappa]B. MMP-1 induction by the ligands for TLR2, TLR3 and TLR5 was inhibited by pretreatment with BAY11-7082 (NF-[kappa]B inhibitor) or SP600125 (JNK inhibitor), whereas MMP-9 expression was inhibited by pretreatment with BAY11-7082, SP600125 or SB203580. These findings demonst...

In vivo and in vitro evidence for epidermal H2O2-mediated oxidative stress in piebaldism

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

Please cite this paper as:In vivo and in vitro evidence for epidermal H2O2-mediated oxidative stress in piebaldism. Experimental Dermatology 2009.Abstract: Piebaldism is characterised by the absence of pigment in patches on the skin, usually present at birth. Mutations in the kit gene are documented. Clinically this disorder can mimic vitiligo. Here, we show for the first time the presence of oxidised pteridine-induced fluorescence in association with H2O2-mediated stress in piebald patches employing Wood's light and in vivo FT-Raman spectroscopy. In situ immunofluorescence data revealed low catalase and methionine sulphoxide reductase A (MSRA) levels whereas thioredoxin reductase and methionine sulphoxide reductase B (MSRB) are not affected. We also show low superoxide dismutase levels in...

Long-term efficacy of etanercept in hidradenitis suppurativa: results from an open-label phase II prospective trial

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

Conclusions: The first treatment course achieved long-term disease remission in almost one-third of patients. The remaining needed a second treatment course but even in that case, their disease severity at restart was significantly lower compared with baseline. (Source: Experimental Dermatology)

IL-6 Stimulates but is not essential for stratum corneum formation and permeability barrier development during gestation

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

In conclusion, exogenous IL-6 accelerates epidermal ontogenesis, but it is not essential for normal epidermal maturation. (Source: Experimental Dermatology)

Human mast cells express androgen receptors but treatment with testosterone exerts no influence on IgE-independent mast cell degranulation elicited by neuromuscular blocking agents

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

Please cite this paper as: Human mast cells express androgen receptors but treatment with testosterone exerts no influence on IgE-independent mast cell degranulation elicited by neuromuscular blocking agents. Experimental Dermatology 2009; x: xx[ndash]xx.Abstract: Women predominate in the anaphylactic reactions to neuromuscular blocking agents (NMBA). The expression of oestrogen receptors has been demonstrated in mast cells and oestrogen treatment can enhance mast cell degranulation, but the influence of androgens remains largely unclear. Our immunocytochemical study showed the expression of androgen receptor (AR) in mast cells isolated from human foreskin as well as in two human mast cell lines, HMC-1 and LAD2. The amount of AR was most abundant in human skin mast cells as determined by r...

Increased subcutaneous adipose tissue impairs dermal function in diet-induced obese mice

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

We examined this issue in HR-1 hairless mice given a high-fat diet (HFD). After having been fed with HFD for 12 weeks, the mice became obese and the subcutaneous adipose tissue layer was significantly thickened, while the dermal layer became significantly thinner than that of control mice fed normal diet. However, the thickness of the dermal layer was not changed in the ear pinna, which lacks a subcutaneous adipose layer, suggesting that increase of subcutaneous adipose tissue may induce dermal changes. The number of dermal fibroblasts in the dermis was significantly reduced in obese mice, although there was no change in gene expression levels of extracellular matrix components, including collagen, hyaluronic acid synthase, fibulin5, fibrillin-1, laminin [beta]1, matrix metalloproteinases ...

CC chemokines as potential immunologic markers correlated with clinical improvement of atopic dermatitis patients by immunotherapy

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

Please cite this paper as: CC chemokines as potential immunologic markers correlated with clinical improvement of atopic dermatitis patients by immunotherapy. Experimental Dermatology 2009.Abstract: Although immunotherapy is not accepted as a curative treatment for atopic dermatitis (AD), most studies have shown positive effects of immunotherapy on AD patients. The serum levels of CC chemokine ligand 17 (CCL17), CCL22 and CCL18 have been reported to be highly correlated with disease severity, which suggests important roles for CC chemokines in the pathogenesis of AD.Objective: The purpose of this study was to investigate the changes in clinical and immunologic markers before and after immunotherapy and to find which CC chemokines correlate with clinical improvement after immunotherapy with...

Signal transducer and activator of transcription 3 upregulates interleukin-8 expression at the level of transcription in human melanoma cells

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

Please cite this paper as: Signal transducer and activator of transcription 3 upregulates interleukin-8 expression at the level of transcription in human melanoma cells. Experimental Dermatology 2009.Abstract: Many melanoma cells continuously produce interleukin-8 (IL-8). The involvement of signal transducer and activator of transcription 3 (STAT3) in the constant production of IL-8 in melanoma cells was examined. The level of IL-8 production correlated well with that of the phosphorylated (activated) STAT3 in six human melanoma cell lines. Introduction of the constitutively activated form of STAT3 (STAT3-C) into WM35 melanoma cells, that show low levels of IL-8 and phosphorylated STAT3, enhanced IL-8 production. Knockdown of STAT3 suppressed IL-8 production in WM1205Lu cells that contain ...

Tumor necrosis factor-α processing inhibitor-1 inhibits skin fibrosis in a bleomycin-induced murine model of scleroderma

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

In this study, we found that sTNFRp55 also is increased in the bleomycin (BLM)-induced murine model of SSc. Therefore, we examined the effect of tumor necrosis factor-[alpha] processing inhibitor-1 (TAPI-1), the inhibitor of TNFRp55 sheddase, in this model. TAPI-1 was administered weekly to mice with skin fibrosis induced by daily BLM injections. TAPI-1 significantly suppressed BLM-induced skin thickness and the number of myofibroblasts. It also inhibited the increase of serum sTNFRp55 after 3 weeks of BLM injections. The mRNA expression of collagen type I [alpha]1, transforming growth factor-[beta]1 and alpha smooth muscle actin were decreased by TAPI-1 administration. Taken together, these findings indicate that targeting the TNF[alpha] converting enzyme might be a new type of therapy fo...

Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus

Experimental Dermatology — Tue, 15 Sep 2009 23:00:00 +0100

Please cite this paper as: Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus. Experimental Dermatology 2009.Abstract: Lupus erythematosus (LE) is a heterogeneous disease ranging from skin-restricted manifestations to a progressive multisystem disease. The specific skin lesions include chronic cutaneous, subacute cutaneous and acute cutaneous LE. Both genetic and environmental factors are involved in the development of LE. However, reports on the genetic background of cutaneous lupus erythematosus (CLE) forms, namely discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE), are sparse. We investigated whether the known systemic LE (SLE) susceptibility genes also predispose to CLE. Altogether, 219 ...

Serum levels of IL-18 and sIL-2R in patients with alopecia areata receiving combined therapy with oral cyclosporine and steroids

Experimental Dermatology — Mon, 14 Sep 2009 23:00:00 +0100

In conclusion, increased serum sIL-2R level and lower IL-18 level at baseline was associated with a poor prognosis in patients with AA. (Source: Experimental Dermatology)

Application of stereology to dermatological research

Experimental Dermatology — Mon, 14 Sep 2009 23:00:00 +0100

Please cite this paper as: Application of stereology to dermatological research. Experimental Dermatology 2009.Abstract: Stereology is a set of mathematical and statistical tools to estimate three-dimensional (3-D) characteristics of objects from regular two-dimensional (2-D) sections. In medicine and biology, it can be used to estimate features such as cell volume, cell membrane surface area, total length of blood vessels per volume tissue and total number of cells. The unbiased quantification of these 3-D features allows for a better understanding of morphology in vivo compared with 2-D methods. This review provides an introduction to the field of stereology with specific emphasis on the application of stereology to dermatological research by supplying a short insight into the theoretica...

Enhanced T-cell activation by immature dendritic cells loaded with HSP70-expressing heat-killed melanoma cells

Experimental Dermatology — Mon, 14 Sep 2009 23:00:00 +0100

In conclusion, HSP70-expressing melanoma cells could be generated by heat-killing. Loading iDCs with heat-killed melanoma cells resulted in a superior priming of autologous T cells in vitro. (Source: Experimental Dermatology)

The potential role of c-Jun activation in patients with cutaneous lichen planus

Experimental Dermatology — Mon, 14 Sep 2009 23:00:00 +0100

Please cite this paper as: The potential role of c-Jun activation in patients with cutaneous lichen planus. Experimental Dermatology 2009.Abstract: c-Jun, a component of the activating protein-1 transcription factor family, has been known to play an important role in the control of cell proliferation. It is also suspected to be a critical mediator of tumor promotion. However, investigations of c-Jun activation patterns in inflammatory and inflammatory transforming skin diseases have not been described so far. In this work, we show the c-Jun activation pattern in skin samples of patients with cutaneous lichen planus (LP), squamous cell carcinoma (SCC), psoriasis and normal skin using an immunohistochemical approach and Western blot analysis. In addition, we studied the c-Jun activation patt...

Isolation of human eosinophils: microbead method has no impact on IL-5 sustained viability

Experimental Dermatology — Mon, 14 Sep 2009 23:00:00 +0100

Conclusions: Multi-antibody eosinophil isolation represents a substantial advantage over anti-CD-16 microbeads when isolating large numbers of eosinophils from concentrated leucocyte preparations. No differential survival was observed. While appropriate consideration of methods is always crucial, multi-antibody eosinophil isolation should not be abandoned completely. (Source: Experimental Dermatology)

Fetuin-A promotes primary keratinocyte migration: independent of epidermal growth factor receptor signalling

Experimental Dermatology — Mon, 14 Sep 2009 23:00:00 +0100

In this study, we found that in human newborn foreskin, a high level of fetuin-A protein is detected throughout the dermis. However, in adult skin a low level of fetuin-A is observed throughout the epidermal and dermal layers, except at regions surrounding hair follicles and at the epidermal-dermal junction where the level of fetuin-A is relatively high. Fetuin-A significantly induces actin-rich protrusions in human primary keratinocytes. Interestingly, blockade of epidermal growth factor (EGF) receptor signalling has a limited effect on fetuin-A promoted 'wound closure' on primary human keratinocytes, but significantly inhibits fetuin-A's effect on HaCaT cells. These results indicate that high levels of fetuin-A may partially contribute to less scar formation in newborn foreskin and that ...

Comparative in situ topoproteome analysis reveals differences in patch test-induced eczema: cytotoxicity-dominated nickel versus pleiotrope pollen reaction

Experimental Dermatology — Mon, 14 Sep 2009 23:00:00 +0100

Please cite this paper as: Comparative in situ topoproteome analysis reveals differences in patch test-induced eczema: cytotoxicity-dominated nickel versus pleiotrope pollen reaction. Experimental Dermatology 2009.Abstract: A subgroup of patients with atopic eczema develops acute eczematous reactions to type I allergy-inducing agents such as pollen that clinically resemble type IV allergies induced by haptens like metal ions. To clarify the underlying immunologic mechanisms, this study was designed to map the inflammatory in situ topoproteome of eczematous responses to grass/birch pollen and nickel by using atopy patch test (APT) and nickel patch test (NPT) as an appropriate clinical model, respectively. Biopsies from NPT (n = 6) and APT (n = 6) with positive reactions at 72 h were analyse...

Erratum

Experimental Dermatology — Mon, 14 Sep 2009 23:00:00 +0100

(Source: Experimental Dermatology)

Comment on: Tattooing of skin results in transportation and light-induced decomposition of tattoo pigments

Experimental Dermatology — Tue, 08 Sep 2009 23:00:00 +0100

Please cite this paper as: Comment on: Tattooing of skin results in transportation and light-induced decomposition of tattoo pigments. Experimental Dermatology 2009.Abstract: Decorative tattoos have become a common feature of many societies. Their popularity appears mainly driven by fashion, and scant attention has been paid to any associated risk. The risks can be associated either with the tattooees' proclivity for risk taking in general, or with the substances used in the tattoos. It is well established that tattoo pigments wander widely in the body after they have been injected, and research now suggests that azo pigments may become mutagenic after exposure to either natural light or laser light. This may not only affect the risk profile of tattoos themselves, but also tattoo removal u...

Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication-competent CD95L adenovirus

Experimental Dermatology — Wed, 02 Sep 2009 23:00:00 +0100

Please cite this paper as: Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication-competent CD95L adenovirus. Experimental Dermatology 2009.Abstract: The high mortality of melanoma demands the development of new strategies, and gene therapy may be considered provided improvements in efficacy and selectivity. Overexpression of the death ligand CD95L/FasL has been shown in previous studies as highly effective for apoptosis induction in melanoma cells. For efficient and selective targeting of melanoma, a conditional replication-competent adenoviral vector was constructed (Ad5-FFE-02), which drives CD95L expression by a tetracycline-inducible promoter. For restricting its replication to melanoma cells, the adenoviral E1A gene is contr...

Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture

Experimental Dermatology — Mon, 31 Aug 2009 23:00:00 +0100

Please cite this paper as: Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture. Experimental Dermatology 2009.Abstract: The organ culture of human scalp hair follicles (HFs) is the best currently available assay for hair research in the human system. In order to determine the hair growth-modulatory effects of agents in this assay, one critical read-out parameter is the assessment of whether the test agent has prolonged anagen duration or induced catagen in vitro. However, objective criteria to distinguish between anagen VI HFs and early catagen in human HF organ culture, two hair cycle stages with a deceptively similar morphology, remain to be established. Here, we develop, document and test an objective classification sy...

Exploring the role of stem cells in cutaneous wound healing

Experimental Dermatology — Thu, 27 Aug 2009 23:00:00 +0100

Please cite this paper as: Exploring the role of stem cells in cutaneous wound healing. Experimental Dermatology 2009Abstract: The skin offers a perfect model system for studying the wound healing cascade, which involves a finely tuned interplay between several cell types, pathways and processes. The dysregulation of these factors may lead to wound healing disorders resulting in chronic wounds, as well as abnormal scars such as hypertrophic and keloid scars. As the contribution of stem cells towards tissue regeneration and wound healing is increasingly appreciated, a rising number of stem cell therapies for cutaneous wounds are currently under development, encouraged by emerging preliminary findings in both animal models and human studies. However, we still lack an in-depth understanding o...

Fondation rene touraine pour la recherche en dermatologie

Experimental Dermatology — Wed, 26 Aug 2009 23:00:00 +0100

(Source: Experimental Dermatology)

Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris

Experimental Dermatology — Tue, 25 Aug 2009 23:00:00 +0100

Please cite this paper as: Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Experimental Dermatology 2009.Abstract: It is the purpose of this viewpoint article to delineate the regulatory network of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signalling during puberty, associated hormonal changes in adrenal and gonadal androgen metabolism, and the impact of dietary factors and smoking involved in the pathogenesis of acne. The key regulator IGF-1 rises during puberty by the action of increased GH secretion and correlates well with the clinical course of acne. In acne patients, associations between serum levels of IGF-1, dehydroepiandrosterone sulphate, dihydrotestosterone, acne lesion cou...

Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function

Experimental Dermatology — Sun, 23 Aug 2009 23:00:00 +0100

Conclusions: Our results demonstrate that TCIs induce negative effects on the skin barrier including permeability and antimicrobial functions, which are mediated by decreasing epidermal lipid synthesis, lamellar body secretion and antimicrobial peptides expression through suppression of cytokine such as IL-1[alpha], therefore co-treatment with PLM would be helpful to overcome these negative effects. (Source: Experimental Dermatology)

Methylation-associated silencing of S100A4 expression in human epidermal cancers

Experimental Dermatology — Sat, 22 Aug 2009 23:00:00 +0100

Please cite this paper as: Methylation-associated Silencing of S100A4 Expression in Human Epidermal Cancers. Experimental Dermatology 2009;Abstract: S100A4 appears important for cancer metastasis and its overexpression is common in a variety of human malignancies, but its status in epidermal cancers remains lesser known. Likewise, E-cadherin downregulation and Wingless (Wnt) activation are frequent cancer-associated alterations, whereas their potential correlations with S100A4 expression in skin lesions have not been characterized. These issues were addressed in the present study using tissue microarray-based immunohistochemical staining, reverse transcriptase polymerase chain reaction and western blotting. Meanwhile, the underlying epigenetic mechanism leading to the altered S100A4 expres...

Tattooing of skin results in transportation and light-induced decomposition of tattoo pigments – a first quantification in vivo using a mouse model

Experimental Dermatology — Sat, 22 Aug 2009 23:00:00 +0100

This study is the first quantitative estimate of the amount of tattoo pigments transported from the skin into the body or decomposed by solar or laser radiation. (Source: Experimental Dermatology)

Photocarcinogenesis and toxicity of benzoyl peroxide in hairless mice after simulated solar radiation

Experimental Dermatology — Sat, 22 Aug 2009 23:00:00 +0100

Abstract: Topical benzoyl peroxide (BPO) gel has long been used to treat acne vulgaris and has recently been combined with clindamycin (BPO-clin). No skin malignancies have been reported after clinical use of BPO, but there has been concern about the possible carcinogenicity of BPO alone and in combination with UV radiation. BPO can promote skin tumorigenesis in a mouse skin chemical carcinogenesis model. As acne vulgaris is frequently localized on sun-exposed areas, we investigated whether BPO or BPO-clin accelerates photocarcinogenesis in combination with simulated solar radiation (SSR) in 12 groups of 25 hairless female C3.Cg/TifBomTac-immunocompetent mice. BPO or BPO-clin was applied topically to the back five times each week, followed by SSR three times each week (2, 3, or 4 standard ...

Improved quality of optical coherence tomography imaging of basal cell carcinomas using speckle reduction

Experimental Dermatology — Fri, 21 Aug 2009 23:00:00 +0100

Conclusion: This OCT speckle reduction method led to improved visualisation and better defined delineations in two BCC lesions. Thus, OCT was improved to a clinically relevant level when imaging BCC lesions. (Source: Experimental Dermatology)

Animal models for autoimmune bullous dermatoses

Experimental Dermatology — Thu, 20 Aug 2009 23:00:00 +0100

Please cite this paper as: Animal models for autoimmune bullous dermatoses. Experimental Dermatology 2009Abstract: Autoimmune bullous dermatoses are a group of severe diseases, which are clinically characterized by blisters and erosions of skin and/or mucous membranes. In order to investigate the pathogenesis of these potentially life-threatening diseases and to develop more specific therapeutic approaches, animal models have been developed that aim to reproduce the clinical, histological and immunopathological findings. We here review established and novel animal models of autoimmune skin blistering diseases and discuss their applications and limitations. (Source: Experimental Dermatology)

What are melanocytes really doing all day long…?

Experimental Dermatology — Wed, 29 Jul 2009 23:00:00 +0100

Please cite this paper as: Plonka et al. What are melanocytes really doing all day long[hellip]? Experimental Dermatology 2009.Abstract: Everyone knows and seems to agree that melanocytes are there to generate melanin [ndash] an intriguing, but underestimated multipurpose molecule that is capable of doing far more than providing pigment and UV protection to skin (1). What about the cell that generates melanin, then? Is this dendritic, neural crest-derived cell still serving useful (or even important) functions when no-one looks at the pigmentation of our skin and its appendages and when there is essentially no UV exposure? In other words, what do epidermal and hair follicle melanocytes do in their spare time [ndash] at night, under your bedcover? How much of the full portfolio of physiolog...

Hidradenitis suppurativa (acne inversa): early inflammatory events at terminal follicles and at interfollicular epidermis*

Experimental Dermatology — Tue, 28 Jul 2009 23:00:00 +0100

Please cite this paper as: Hidradenitis suppurativa (acne inversa): early inflammatory events at terminal follicles and at interfollicular epidermis. Experimental Dermatology 2009.Abstract: Hidradenitis suppurativa (acne inversa) is a chronic suppurative and scarring inflammatory disease with predilection in the apocrine gland-bearing areas. Histological investigations in the 1990s showed keratotic occlusion of the terminal follicle structure to be the initial cause. Our investigations describe and reproduce the morphology and try to figure out very early lesions of HS. A total of 262 operative specimens from 60 patients were investigated by routine histology and 11 operative specimens by immunohistochemistry: HS is dominated by a heterogeneous histological image. 82% of the surgical speci...

In vivo distribution of carotenoids in different anatomical locations of human skin: comparative assessment with two different Raman spectroscopy methods

Experimental Dermatology — Thu, 23 Jul 2009 23:00:00 +0100

Conclusion: The present study supports the hypothesis that antioxidative substances; here carotenoids, are secreted via eccrine sweat glands and/or sebaceous glands to the skin surface. Raman spectroscopic methods are an efficient tool to analyze the distribution of carotenoids in the human skin over time and with the Skin Analyzer over different layers of the epidermis. Resonance Raman spectroscopy is suited to analyze deeper parts of the skin. (Source: Experimental Dermatology)

Regression of established subcutaneous B16-F10 murine melanoma tumors after gef gene therapy associated with the mitochondrial apoptotic pathway

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Please cite this paper as: Regression of established subcutaneous B16-F10 murine melanoma tumors after gef gene therapy associated with the mitochondrial apoptotic pathway. Experimental Dermatology 2009.Abstract: Novel treatment modalities, including gene therapy, are needed for patients with advanced melanoma. We evaluated whether the gef gene, a suicide gene from Escherichia coli, had a significant cytotoxic impact on melanoma in vivo. First, we used a non-viral gene delivery approach (pcDNA3.1/gef) to study the inhibition of melanoma cells (B16-F10) proliferation in vitro. Secondly, we used direct intra-tumoral injection of pcDNA3.1/gef complexed with jetPEI to deliver gef cDNA to rapidly growing murine melanomas. We demonstrated that gef gene not only has an antiproliferative effect on...

T-lymphocyte-induced, fas-mediated apoptosis is associated with early keratinocyte differentiation

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

In this study, we investigated the interaction of T cells and keratinocytes on apoptosis and terminal differentiation using an in vitro co-culture system. Experiments were performed using the HaCaT keratinocyte cell line or normal human epidermal keratinocytes. Activated human peripheral blood-derived T cells were found to induce Fas-dependent keratinocyte apoptosis by up to sixfold. Increased Fas was associated with increased IFN-[gamma]. The T-cell apoptotic signal was found to target preferentially keratinocytes in the very early stages of terminal differentiation, such as those with low levels of [alpha]6-integrin expression, and result in subsequent increased caspase 3 activity. This observation was accompanied by a marked increase in keratinocyte ICAM-1 expression and its ligand LFA-...

Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

In conclusion, zileuton prevents the activation of the leukotriene pathway and enhancement of lipogenesis by AA in human sebocytes in vitro. (Source: Experimental Dermatology)

Why do melanomas get so dark?

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Please cite this paper as: Why do melanomas get so dark? Experimental Dermatology 2009.Abstract: Cutaneous malignant melanomas often exhibit pigmented regions that are darker than the surrounding skin. While melanoma cells are the original source of the melanin, keratinocytes and melanophages also contribute to the tumor colour because they contain melanin obtained from melanoma cells. However, little is known of the origin of darkly pigmented melanoma cells or of the molecular pathways regulating their melanin production. Here we discuss observations that dark melanoma cells emerge from within populations of melanoma in situ and that, in addition to producing abundant dark pigment, they appear to be undergoing autophagy. Moreover, autophagy appears to be a common trait of invasive melanom...

Does erythropoietin modulate human hair follicle melanocyte activities in situ?

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Please cite this paper as: Does erythropoietin modulate human hair follicle melanocyte activities in situ? Experimental Dermatology 2009.Abstract: Erythropoietin (EPO) is now appreciated for not only drive erythopoiesis, but also to exert additional functions. Since we had previously shown that human hair follicles (HFs) are both an extra-renal source and an extra-medullary target of EPO, we have now studied whether one such function is the regulation of HF pigmentation. Human anagen VI HFs were treated with EPO (100 IU/ml) in serum-free organ culture. Unexpectedly, we noticed greatly divergent pigmentary effects of EPO, since both up- and down-regulation of HF melanin content and tyrosinase activity in situ was seen in HF derived from different individuals. These divergent effects could n...

Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Conclusion: The tested silver-loaded seaweed fibre can be regarded as safe and seams to be suited for application in bio-active textiles in atopic dermatitis based on its positive in vivo activity. (Source: Experimental Dermatology)

Injury downregulates the expression of the human cathelicidin protein hCAP18/LL-37 in atopic dermatitis

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Please cite this paper as: Injury downregulates the expression of the human cathelicidin protein hCAP18/LL-37 in atopic dermatitis. Experimental Dermatology 2009.Abstract: Reduced production of antimicrobial peptides was proposed to contribute to susceptibility for skin infections in atopic dermatitis (AD). Focusing on the human cathelicidin protein, hCAP18, the aim of the present study was to explore whether reduced hCAP18 expression is a constitutive trait in AD and if established inducers affect the expression of hCAP18 in the skin of AD. First, we compared levels of hCAP18 mRNA between lesional skin in AD and psoriasis and verified significantly lower expression of hCAP18 mRNA in AD. In non-lesional skin, however, there was no difference between AD, psoriasis and healthy, indicating th...

Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo-epidermal separation of 4 mm human skin biopsies

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Please cite this paper as: Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo-epidermal separation of 4 mm human skin biopsies. Experimental Dermatology 2009.Abstract: To obtain a separation of the epidermal and dermal compartments to examine compartment specific biological mechanisms in the skin, we incubated 4 mm human skin punch biopsies in ammonium thiocyanate. We wanted to test (i) the histological quality of the dermo-epidermal separation obtained by different incubation times; (ii) the amount and quality of extractable epidermal RNA and (iii) its impact on sample RNA expression profiles assessed by large-scale gene expression microarray analysis in both normal and inflamed skin. At 30-min incubation, the split between dermis and epidermis was not alway...

Liver X receptor expression in human melanocytes, does it have a role in the pathogenesis of vitiligo?

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Please cite this paper as: Liver X receptor expression in human melanocytes, does it have a role in the pathogenesis of vitiligo? Experimental Dermatology 2009.Abstract: Vitiligo is a common, non-contagious disorder. The basic pathogenesis of vitiligo generally, or for any of the putative subsets of vitiligo, remains unknown. The liver X receptors (LXRs), LXR-[alpha] and LXR-[beta] are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Important genes involved in regulation of melanocytes are target genes of LXRs; it can be speculated that LXRs might be playing an important role in pathogenesis of pigmentary disorders. We have demonstrated in this study that there is expression of LXR-[alpha]/[beta] by human melanocytes at both transcriptional an...

Biofilm formation on rat skin wounds by Pseudomonas aeruginosa carrying the green fluorescent protein gene

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

In conclusion, wound healing of rat acute wounds was unaffected by biofilm formation. (Source: Experimental Dermatology)

The mesenchymal component of hair follicle neogenesis: background, methods and molecular characterization

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Please cite this paper as: The mesenchymal component of hair follicle neogenesis: background, methods and molecular characterization. Experimental Dermatology 2009.Abstract: Hair follicle morphogenesis and regeneration occur by an extensive and collaborative crosstalk between epithelial and mesenchymal skin components. A series of pioneering studies, which revealed an indispensable role of follicular dermal papilla and dermal sheath cells in this crosstalk, has led workers in the field to study in detail the anatomical distribution, functional properties, and molecular signature of the trichogenic dermal cells. The purpose of this paper was to provide a practical summary of the development and recent advances in the study of trichogenic dermal cells. Following a short review of the relevan...

Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Please cite this paper as: Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice. Experimental Dermatology 2009.Abstract: Sharpin-deficient (Sharpincpdm) mutant mice develop a chronic eosinophilic dermatitis. To determine the efficacy of eosinophil-depletion in chronic inflammation, Sharpincpdm mice were treated with anti-IL5 antibodies. Mice treated with anti-IL5 had a 90% reduction of circulating eosinophils and a 50% decrease in cutaneous eosinophils after 10 days compared with sham-treated littermates. Reducing the number of eosinophils resulted in increased severity of alopecia and erythema and a significant increase in epidermal thickness. Skin homogenates from mice treated with anti-IL5 had decreased mRNA expression of arylsulfatas...

Analysis of ionizing radiation-induced DNA damage and repair in three-dimensional human skin model system

Experimental Dermatology — Wed, 22 Jul 2009 23:00:00 +0100

Please cite this paper as: Analysis of ionizing radiation-induced DNA damage and repair in three-dimensional human skin model system. Experimental Dermatology 2009.Abstract: Knowledge of cellular responses in tissue microenvironment is crucial for the accurate prediction of human health risks following chronic or acute exposure to ionizing radiation (IR). With this objective, we investigated the radio responses for the first time in three-dimensional (3D) artificial human skin tissue microenvironment after [gamma]-rays radiation. IR-induced DNA damage/repair response was assessed by immunological analysis of well-known DNA double strand break (DSB) repair proteins, i.e. 53BP1 and phosphorylated ataxia telangiectasia mutatedser1981 (ATMser1981). Efficient 53BP1 and phosphorylated ATM foci f...

Heat-killed Propionibacterium acnes is capable of inducing inflammatory responses in skin

Experimental Dermatology — Mon, 13 Jul 2009 23:00:00 +0100

Please cite this paper as: Heat-killed Propionibacterium acnes is capable of inducing inflammatory responses in skin. Experimental Dermatology 2009.Abstract: The etiology of acne is a complex process, and acne is one of the most common skin disorders affecting millions of people. The pathogenesis of acne is closely associated with the bacterium, Propionibacterium acnes which was previously known as Corynebacterium parvum. Both viable and non-viable P. acnes/C. parvum have been shown to induce an immunostimulatory effect in vivo, suggesting that even dead bacteria continue to activate an inflammatory response. Acne treatments with lasers or devices, induce a bactericidal effect through heat generation which may not address the immunogenic activity of P. acnes and the resulting acne inflamma...

Bifidobacterium longum lysate, a new ingredient for reactive skin

Experimental Dermatology — Mon, 13 Jul 2009 23:00:00 +0100

Please cite this paper as: Bifidobacterium longum lysate, a new ingredient for reactive skin. Experimental Dermatology 2009.Abstract: Reactive skin is characterized by marked sensitivity to physical (heat, cold, wind) or chemical (topically applied products) stimuli and by the impairment of the skin barrier's ability to repair itself. Several lines of evidence suggest that beyond their capacity to positively influence the composition of intestinal microbiota, some probiotic bacteria can modulate the immune system both at local and systemic levels, thereby improving immune defense mechanisms and/or down-regulating immune disorders such as allergies and intestinal inflammation. Several recent human clinical trials clearly suggest that probiotic supplementation might be beneficial to the skin...

Leptin and the skin: a new frontier

Experimental Dermatology — Wed, 08 Jul 2009 23:00:00 +0100

Please cite this paper as: Leptin and the skin: a new frontier. Experimental Dermatology 2009.Abstract: Here, we examine the currently available information which supports that the adipokine, leptin, is a major player in the biology and pathology of mammalian skin and its appendages. Specifically, the potent metabolic effects of leptin and its mimetics may be utilized to improve, preserve and restore skin regeneration and hair cycle progression, and may halt or even partially reverse some aspects of skin ageing. Since leptin can enhance mitochondrial activity and biogenesis, this may contribute to the wound healing-promoting and hair growth-modulatory effects of leptin. Leptin dependent intracellular signalling by the Janus kinase 2 dependent signal transducer and activator of transcriptio...

Extrinsic ageing in the human skin is associated with alterations in the expression of hyaluronic acid and its metabolizing enzymes

Experimental Dermatology — Tue, 07 Jul 2009 23:00:00 +0100

In this study, we investigated the expression of HA and its metabolizing enzymes in photoexposed and photoprotected human skin tissue specimens, obtained from the same patient. Total GAG were isolated, characterized using specific GAG-degrading enzymes and separated by electrophoresis on cellulose acetate membranes and polyacrylamide gels. Quantitation of HA in total GAG was performed using ELISA. Gene expression of hyaluronan synthases (HAS), hyaluronidases (HYAL) and HA receptors CD44 and receptor for HA-mediated motility (RHAMM) was assessed by RT-PCR. We detected a significant increase in the expression of HA, of lower molecular mass, in photoexposed skin as compared with photoprotected skin. This increase was associated with a significant decrease in the expression of HAS1 and an incr...

MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer

Experimental Dermatology — Tue, 07 Jul 2009 23:00:00 +0100

Please cite this paper as: MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer. Experimental Dermatology 2009.Abstract: The squamous cell cancers (SCC) of renal transplant recipients are more aggressive and metastasize earlier than those of the non-immunocompromised population. Matrix metalloproteinases (MMPs) have a central role in tumor initiation, invasion and metastasis. Our aim was to compare the expression of MMPs-10, -12 and -21 in SCCs from immunosuppressed (IS) and control patients and the contribution of MMPs-10 and -21 to SCC development in the FVB/N-Tg(KRT5-Nfkbia)3Rto mouse line. Immunohistochemical analysis of 25 matched pairs of SCCs, nine of Bowen's disease and timed back skin biopsies of mice with selective inhibition of Rel/NF-[kappa]B signalling we...

MAP17 is associated with the T-helper cell cytokine-induced down-regulation of filaggrin transcription in human keratinocytes

Experimental Dermatology — Tue, 07 Jul 2009 23:00:00 +0100

Please cite this paper as: MAP17 is associated with the T-helper cell cytokine-induced down-regulation of filaggrin transcription in human keratinocytes. Experimental Dermatology 2009.Abstract: In the meta-analysis of public microarray databases for different skin diseases, we revealed seven commonly up-regulated genes, DSG3, KRT6, MAP17, PLSCR1, RPM2, SOD2 and SPRR2B. We postulated that the genes selected from the meta-analysis may be potentially associated with the abnormal keratinocyte differentiation. To demonstrate this postulation, we alternatively evaluated whether the genes of interest in the meta-analysis can be regulated by T-helper (Th) cell cytokines in normal human epidermal keratinocytes (NHEK). We found that MAP17 was significantly up-regulated in response to interferon-[gam...

Keratinocytes efficiently process endogenous antigens for cytotoxic T-cell mediated lysis

Experimental Dermatology — Tue, 07 Jul 2009 23:00:00 +0100

Please cite this paper as: Keratinocytes efficiently process endogenous antigens for cytotoxic T-cell-mediated lysis. Experimental Dermatology 2009.Abstract: The generation of a robust CD8+ cytotoxic T lymphocyte (CTL) response is a key feature of many immunotherapeutic strategies against epithelial tumors and virally infected epithelial tissue. However, surprisingly few studies have addressed whether primary epithelial cells, expressing defined endogenous antigens, are good targets for CTL-mediated lysis. Here, we show that primary keratinocytes (KCs), expressing endogenous ovalbumin (OVA) as a transgene, present measurable H-2Kb/SIINFEKL complexes at the cell surface and are killed by OVA-specific CTL. Target cell lysis was comparable with a more traditional CTL target cell, EL4, and was...

Effector pathways during eczematous dermatitis: where inflammation meets cell death

Experimental Dermatology — Mon, 06 Jul 2009 23:00:00 +0100

Please cite this paper as: Effector pathways during eczematous dermatitis: Where inflammation meets cell death. Experimental Dermatology 2009.Abstract: During eczematous skin inflammation, the main constituents of the skin, keratinocytes (KC), play an important role in inducing and shaping the immunological response to environmental stimuli. This review focuses on the epidermal inflammation caused by keratinocyte-T cell interactions arising from a disturbed barrier function of the skin. In eczematous dermatitis, activated dermis- and epidermis-infiltrating T cells target KC for apoptosis. In turn, damaged KC respond by secreting inflammatory mediators, thus effecting further recruitment of immunocytes to inflamed skin. Further advances will come from identification of the immunoregulatory ...

Apoptolysis: a novel mechanism of skin blistering in pemphigus vulgaris linking the apoptotic pathways to basal cell shrinkage and suprabasal acantholysis

Experimental Dermatology — Thu, 25 Jun 2009 23:00:00 +0100

Please cite this paper as: Apoptolysis: a novel mechanism of skin blistering in pemphigus vulgaris linking the apoptotic pathways to basal cell shrinkage and suprabasal acantholysis. Experimental Dermatology 2009.Abstract: Understanding the acantholytic pathways leading to blistering in pemphigus vulgaris (PV) is a key to development of novel treatments. A novel paradigm of keratinocyte damage in PV, termed apoptolysis, links the suprabasal acantholytic and cell death pathways to basal cell shrinkage rendering a 'tombstone' appearance to PV lesions. In contrast to apoptolysis, the classic keratinocyte apoptosis mediating toxic epidermal necrolysis causes death and subsequent sloughing of the entire epidermis. Apoptolysis includes five consecutive steps. (1) Binding of autoantibodies to PV ...

Hydrophilic and lipophilic moisturizers have similar penetration profiles but different effects on SC water distribution in vivo

Experimental Dermatology — Wed, 24 Jun 2009 23:00:00 +0100

In this study, both types of moisturizers were applied on volunteers for 3 h, after which the relative amount of moisturizer and the water distribution in the SC were determined using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy in combination with tape-stripping. The results show that while hydrophilic moisturizers penetrate much more readily than lipophilic moisturizers, the latter are abundantly present in the upper regions of the SC. It was also observed that a 3-h treatment with lipophilic moisturizer did not result in increased water levels in the SC, whereas hydrophilic moisturizers retained water where they are located. The results suggest that upon prolonged application, adequate amounts of moisturizer can be obtained in those regions where they ...

An improved method of human keratinocyte culture from skin explants: cell expansion is linked to markers of activated progenitor cells

Experimental Dermatology — Wed, 24 Jun 2009 23:00:00 +0100

Please cite this paper as: An improved method of human keratinocyte culture from skin explants: cell expansion is linked to markers of activated progenitor cells. Experimental Dermatology 2009.Abstract: Human keratinocyte primary cultures are commonly established by tissue dissociation and often rely on feeder cell supports and culture medium that is not defined. Further, contamination by unwanted fibroblasts can be problematic. Here, we developed a skin explant method for growing primary keratinocytes that was rapid, simple, and reliably generated keratinocyte cultures free of fibroblast contamination. The process capitalized on the observation that fibroblasts migrate out of adult skin explants later than epidermal cells, allowing the early harvesting of keratinocytes by trypsinization. ...

Inhibition of 12-LOX and COX-2 reduces the proliferation of human epidermoid carcinoma cells (A431) by modulating the ERK and PI3K-Akt signalling pathways

Experimental Dermatology — Tue, 23 Jun 2009 23:00:00 +0100

Please cite this paper as: Inhibition of 12-LOX and COX-2 reduces the proliferation of human epidermoid carcinoma cells (A431) by modulating the ERK and PI3K-Akt signalling pathways. Experimental Dermatology 2009.Abstract: Eicosanoids, the oxygenated metabolites of arachidonic acid (AA), mediate a variety of human diseases, such as cancer, inflammation and arthritis. To evaluate the role of eicosanoids in epidermoid carcinoma, the expression of AA metabolizing enzymes, such as lipoxygenases (LOXs) and cyclooxygenases (COXs), was analysed in a human epidermoid carcinoma cell line (A431). These studies revealed overexpression of 12-R-LOX and COX-2 in A431 cells. Baicalein (a 12-LOX inhibitor) and celecoxib (a COX-2 inhibitor) significantly reduced thymidine incorporation, whereas 12-(R)-HETE...

An imbalance in Akt/mTOR is involved in the apoptotic and acantholytic processes in a mouse model of pemphigus vulgaris