American Journal of Respiratory Cell and Molecular Biology
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Highlights of the november issue.
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PMID: 19843709 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - October 23, 2009 Category: Molecular Biology Authors: Adler KB, Matalon S Tags: Am J Respir Cell Mol Biol Source Type: journals
An evolutionary perspective on chronic obstructive pulmonary disease.
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PMID: 19843710 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - October 23, 2009 Category: Molecular Biology Authors: Aoshiba K, Nagai A Tags: Am J Respir Cell Mol Biol Source Type: journals
TSLP Induces Chemotactic and Pro-survival Effects in Eosinophils: Implications in Allergic Inflammation.
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Thymic stromal lymphopoietin (TSLP) is highly expressed by bronchial epithelial cells and skin keratinocytes in allergic diseases. TSLP acts as a master switch for allergic inflammation through the activation of dendritic cells and mast cells for initiating inflammatory type 2 T-helper lymphocyte (Th2) responses. To elucidate the immunological cascades of epithelium/keratinocyte-eosinophil mediated allergic inflammation, we examined the modulating effects of TSLP on human eosinophils. Expression of TSLP receptor complex was detected by RT-PCR, flow cytometry and Western blot. Adhesion molecules, cytokine and chemokines...
Source: American Journal of Respiratory Cell and Molecular Biology - October 19, 2009 Category: Molecular Biology Authors: Wong CK, Hu S, Cheung PF, Lam CW Tags: Am J Respir Cell Mol Biol Source Type: journals
Protein Thiol Oxidation in Murine Airway Epithelial Cells in Response to Naphthalene or Diethyl Maleate.
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Naphthalene is a semi-volatile aromatic hydrocarbon to which humans are exposed from a variety of sources. Naphthalene results in acute cytotoxicity to respiratory epithelium in rodents. Cytochrome P450-dependent metabolic activation to form reactive intermediates and loss of soluble cellular thiols (glutathione) are critical steps in naphthalene toxicity, but the precise mechanisms by which this chemical results in cellular injury remain unclear. Protein thiols are likely targets of reactive naphthalene metabolites. Loss of these, either through adduction or thiol oxidation mechanisms, may be important underlying mech...
Source: American Journal of Respiratory Cell and Molecular Biology - October 19, 2009 Category: Molecular Biology Authors: Spiess PC, Morin D, Williams CR, Buckpitt AR Tags: Am J Respir Cell Mol Biol Source Type: journals
Acute Lung Injury but not Sepsis is Associated with Increased Colony Formation by Peripheral Blood Mononuclear Cells.
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Acute lung injury (ALI) and severe sepsis are common critical illnesses associated with mobilization of bone marrow-derived cells into circulation. By identifying and determining these cellsâ functional characteristics, unique prognostic biomarkers can be developed to help investigators understand mechanisms underlying the pathophysiology of these disorders. We previously demonstrated increased colony forming unit (CFU) ability of circulating peripheral blood mononuclear cells (PBMCs) from patients with ALI compared to healthy controls that also correlated with improved survival. Here we hypothesized that increase...
Source: American Journal of Respiratory Cell and Molecular Biology - October 19, 2009 Category: Molecular Biology Authors: Burnham EL, Mealer M, Gaydos J, Majka S, Moss M Tags: Am J Respir Cell Mol Biol Source Type: journals
MMP-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-induced Airway Inflammation.
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Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic mediators by cleavage. MMP-19 is a newly described MMP and preferentially cleaves matrix proteins such as collagens and tenascin-C. The role of MMP-19 in asthma has not been described to date. The purpose of the present study was to assess MMP-19 expression in a murine asthma model and to address biological effects of MMP-19 deficiency in mice. Allergen-exposed wild-type (WT) mice displayed an increased expression of MMP-19 ...
Source: American Journal of Respiratory Cell and Molecular Biology - October 19, 2009 Category: Molecular Biology Authors: Gueders MM, Hirst SJ, Quesada-Calvo F, Paulissen G, Hacha J, Gilles C, Gosset P, Louis R, Foidart JM, Lopez-Otin C, Noël A, Cataldo DD Tags: Am J Respir Cell Mol Biol Source Type: journals
Expression of TRPC6 Channels in Human Lung Macrophages.
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This study examined the expression and function of transient receptor potential (TRP) channels in human macrophages. Human alveolar macrophages and lung tissue macrophages expressed increased mRNA and protein for TRPC6 when compared with monocytes and monocyte-derived-macrophages. Moreover, TRPC6 mRNA expression was significantly elevated in alveolar macrophages from COPD patients compared to control subjects. There were no differences in mRNA for TRPC3 or TRPC7. Although mRNA for TRPM2 and TRPV1 was detected in these cells, protein expression could not be determined. Fractionation of lung derived-macrophages demonstrated ...
Source: American Journal of Respiratory Cell and Molecular Biology - October 19, 2009 Category: Molecular Biology Authors: Finney-Hayward TK, Popa O, Bahra P, Li S, Poll CT, Gosling M, Nicholson AG, Russell RE, Kon OM, Jarai G, Westwick J, Barnes PJ, Donnelly LE Tags: Am J Respir Cell Mol Biol Source Type: journals
Human Rhinovirus Infection Upregulates MMP-9 Production in Airway Epithelial Cells via NF-{kappa}B.
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In this study we sought, firstly, to determine whether HRV infection modulated the expression of MMP-9 and its highest affinity inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 and, secondly, to explore the mechanism by which this occurs. In vitro studies, using RT-PCR, ELISA, zymography and a fluorescent activity assay, demonstrated that MMP-9 mRNA, protein and activity were increased upon infection with HRV, while TIMP-1 mRNA and protein remained unchanged. These results were then verified in vivo, using nasal lavage samples obtained from subjects with confirmed rhinovirus infections. HRV infections have been sh...
Source: American Journal of Respiratory Cell and Molecular Biology - September 24, 2009 Category: Molecular Biology Authors: Tacon CE, Wiehler S, Holden NS, Newton R, Proud D, Leigh R Tags: Am J Respir Cell Mol Biol Source Type: journals
Characterization of PCEng2 a {beta}-1,3-Endoglucanase Homologue in Pneumocystis carinii with Activity in Cell Wall Regulation.
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In this study we have identified a Pneumocystis beta-1,3-endoglucanase gene (PCEng2) that is demonstrated to play a significant role in cell wall regulation. The full sequence of the gene revealed a 2.2kb open reading frame with conserved amino acid domains homologous to similar fungal glycosyl hydrolases (GH family 81). The gene transcript showed upregulation in cystic isolates and the expressed protein was detected within both cyst and trophic forms. Complementation assays in Eng2 deleted S. cerevisiae strains showed restoration of the cell wall separation defect during proliferation, demonstrating the importance of PCEn...
Source: American Journal of Respiratory Cell and Molecular Biology - September 24, 2009 Category: Molecular Biology Authors: Villegas LR, Kottom TJ, Limper AH Tags: Am J Respir Cell Mol Biol Source Type: journals
Rhinovirus-induced Exacerbations of Asthma - How is the {beta}2-adrenoceptor Implicated?
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Conclusions: This study shows that epithelial infection with RV induces a decrease of ss2AR function on airway smooth muscle cells, potentially explaining the clinical observation of loss of ss2AR agonist function during RV-induced asthma exacerbations.
PMID: 19783788 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - September 24, 2009 Category: Molecular Biology Authors: Trian T, Ge Q, Moir LM, Burgess JK, Kuo C, King NJ, Reddel HK, Black JL, Oliver BG, McParland BE Tags: Am J Respir Cell Mol Biol Source Type: journals
Involvement of IL-13 in Tobacco Smoke Induced Changes in the Structure and Function of Rat Intrapulmonary Airways.
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Chronic obstructive pulmonary disease (COPD) involves disease of small airways with an increase in airway smooth muscle sensitivity to spasmogens and with structural changes described as airway remodeling. We have investigated the effect tobacco smoke (TS) exposure on the structure and function of small airways in rats, and have also studied the role of interleukin (IL)-13 in this response. Precision-cut lung slices (230-280 microm) were prepared from male Sprague-Dawley rats after acute (3 days) or chronic (8 or 16 weeks) daily exposure to TS, or air. Carbachol (CCh) and 5-hydroxytryptamine (5HT) concentration-respons...
Source: American Journal of Respiratory Cell and Molecular Biology - September 24, 2009 Category: Molecular Biology Authors: Cooper PR, Poll CT, Barnes PJ, Sturton RG Tags: Am J Respir Cell Mol Biol Source Type: journals
DNA Double Strand Breaks by Asbestos, Silica and Titanium dioxide: Possible Biomarker of Carcinogenic Potential?
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DNA double strand breaks (DNA DSBs) are a very rapid response to DNA damage that occurs in cells subjected to radiation, exposure to toxic substances, and other environmental stresses. The inability to repair these breaks can lead to carcinogenesis. One of the earliest responses to DNA DSBs is the phosphorylation of a histone, H2AX, at serine 139, yielding a focal product (gamma-H2AX) that can be detected by a fluorescent antibody. A study was undertaken to compare the induction of DNA DSBs in normal (SAE) and cancer cells (A549) after exposure to asbestos (crocidolite), a proven carcinogen, silica a suspected carcinog...
Source: American Journal of Respiratory Cell and Molecular Biology - September 24, 2009 Category: Molecular Biology Authors: Msiska Z, Pacurari M, Mishra A, Leonard SS, Castranova V, Vallyathan V Tags: Am J Respir Cell Mol Biol Source Type: journals
Bacterial Lipopolysaccharide Enhances PDGF Signaling and Pulmonary Fibrosis in Rats Exposed to Carbon Nanotubes.
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Engineered multi-walled carbon nanotubes (MWCNT) represent a possible health risk for pulmonary fibrosis due to their fiber-like shape and potential for persistence in the lung. We postulated that bacterial lipopolysaccharide (LPS), a ubiquitous agent in the environment that causes lung inflammation, would enhance fibrosis caused by MWCNT. Rats were exposed to LPS and then intratracheally instilled with MWCNT or carbon black (CB) nanoparticles 24 hrs later. Pulmonary fibrosis was observed 21 days post-MWCNT exposure, but not with CB. LPS alone caused no fibrosis but enhanced MWCNT-induced fibrosis. LPS plus CB did not ...
Source: American Journal of Respiratory Cell and Molecular Biology - September 7, 2009 Category: Molecular Biology Authors: Cesta MF, Ryman-Rasmussen JP, Wallace DG, Masinde T, Hurlburt G, Taylor AJ, Bonner JC Tags: Am J Respir Cell Mol Biol Source Type: journals
Mechanisms of Neutrophil Accumulation in the Lungs Against Bacteria.
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Bacterial lung diseases are a major cause of morbidity and mortality both in immunocompromised and immunocompetent individuals. Neutrophil accumulation, a pathological hallmark of bacterial diseases, is critical to host defense, but may also cause ALI/ARDS. Toll-like receptors, NOD-like receptors, transcription factors, cytokines, and chemokines play essential roles in neutrophil sequestration in the lungs. This review highlights our current understanding of the role of these molecules in the lungs during bacterial infection and their therapeutic potential. We also discuss emerging data on cholesterol and ethanol as en...
Source: American Journal of Respiratory Cell and Molecular Biology - September 7, 2009 Category: Molecular Biology Authors: Balamayooran G, Batra S, Fessler MB, Happel KI, Jeyaseelan S Tags: Am J Respir Cell Mol Biol Source Type: journals
Adrenomedullin Promotes Lung Angiogenesis, Alveolar Development and Repair.
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Bronchopulmonary dysplasia (BPD) and emphysema are significant global health problems at the extreme stages of life. Both are characterized by alveolar simplification and abnormal distal airspace enlargement due to arrested development or loss of alveoli, respectively. Both lack effective treatments. Mechanisms that inhibit distal lung growth are poorly understood. Adrenomedullin (AM), a recently discovered potent vasodilator, promotes angiogenesis and has protective effects on the cardiovascular and respiratory system. Its role in the developing lung is unknown. We hypothesized that AM promotes lung angiogenesis and a...
Source: American Journal of Respiratory Cell and Molecular Biology - September 7, 2009 Category: Molecular Biology Authors: Vadivel A, Abozaid S, van Haaften T, Sawicka M, Eaton F, Chen M, Thebaud B Tags: Am J Respir Cell Mol Biol Source Type: journals
The Cytokine Network in COPD.
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Multiple cytokines play a role in the orchestration of inflammation in inflammatory airway diseases, such as COPD, through the recruitment, activation and survival of inflammatory cells. Lymphokines secreted from T-cells regulate the pattern of inflammation, whereas proinflammatory cytokines amplify and perpetuate the inflammatory response. Multiple chemokines recruit inflammatory cells from the circulation into the lungs and many growth factors maintain this inflammation and lead to characteristic structural changes in the airways. There are several therapeutic approaches that target cytokine-mediated inflammation in ...
Source: American Journal of Respiratory Cell and Molecular Biology - August 27, 2009 Category: Molecular Biology Authors: Barnes PJ Tags: Am J Respir Cell Mol Biol Source Type: journals
Potential Role of Endothelin-1 in Pulmonary Fibrosis: from the Bench to the Clinic.
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Endothelin-1 (ET-1) plays a central role in lung fibrosis. It is released in the lung at low concentrations from the endothelium, epithelium and vascular smooth muscle cells and orchestrates a variety of effects.1, 2 In the context of wound healing, ET-1 acts with other profibrotic mediators to recruit fibroblasts and allow for their differentiation to contractile myofibroblasts.3 These specialized cells in turn lay down fibrotic tissue and contract at the site of lesions to restore tissue integrity. Apoptosis and reversion to quiescence ensues.4 However, in diseases of the lung such as idiopathic pulmonary fibrosis (I...
Source: American Journal of Respiratory Cell and Molecular Biology - August 27, 2009 Category: Molecular Biology Authors: Ross B, D'Orleans-Juste P, Giaid A Tags: Am J Respir Cell Mol Biol Source Type: journals
Poly I:C Stimulates Versican Accumulation in the Extracellular Matrix Promoting Monocyte Adhesion.
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Viral infections are known to exacerbate asthma and other lung diseases where chronic inflammatory processes are implicated, but the mechanism is not well understood. The viral mimetic, polyinosine-polycytidylic acid (poly I:C), causes accumulation of a versican- and hyaluronan-enriched extracellular matrix (ECM) by human lung fibroblasts (HLF) with increased capacity for monocyte adhesion. The 5-fold increase in versican retention in this ECM is due to altered compartmentalization with decreased degradation of cell-layer associated versican rather than an increase in total accumulation in the culture. This is consiste...
Source: American Journal of Respiratory Cell and Molecular Biology - August 27, 2009 Category: Molecular Biology Authors: Potter-Perigo S, Johnson PY, Evanko SP, Chan CK, Braun KR, Wilkinson TS, Altman LC, Wight TN Tags: Am J Respir Cell Mol Biol Source Type: journals
Beta6 Integrin Subunit Deficiency Alleviates Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia.
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Pulmonary inflammation is associated with the development of bronchopulmonary dysplasia (BPD) in premature infants. We have previously shown that perinatal pulmonary expression of human interleukin-1beta (IL-1beta) is sufficient to cause a lung disease similar to BPD, characterized by inflammation, impaired alveolarization, poor postnatal growth, and increased mortality in infant mice. The alphavbeta6 integrin plays a critical role in regulating inflammation in the adult lung. To study the role of the beta6 integrin subunit in neonatal inflammatory lung disease, we compared the pulmonary development in IL-1beta-express...
Source: American Journal of Respiratory Cell and Molecular Biology - August 27, 2009 Category: Molecular Biology Authors: Hogmalm A, Sheppard D, Lappalainen U, Bry K Tags: Am J Respir Cell Mol Biol Source Type: journals
Serotonin Decreases Alveolar Epithelial Fluid Transport via a Direct Inhibition of the Epithelial Sodium Channel ENaC.
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Hypoxia and epithelial stretch that are commonly observed in patients with acute lung injury have been shown to promote the release of serotonin in vitro. However, whether serotonin contributes to the decrease of the alveolar epithelial fluid transport, which is a hallmark of lung injury, is unknown. Thus, we investigated the effect of serotonin on ion and fluid transport across the alveolar epithelium. Serotonin caused a dose-dependent inhibition of the amiloride-sensitive current across primary rat and human alveolar epithelial (ATII) cell monolayers, but did not affect Na+/K+ ATPase function. Furthermore, we found t...
Source: American Journal of Respiratory Cell and Molecular Biology - August 27, 2009 Category: Molecular Biology Authors: Goolaerts A, Roux J, Ganter MT, Shlyonsky V, Chraibi A, Stéphane R, Mies F, Matthay MA, Naeije R, Sariban-Sohraby S, Howard M, Pittet JF Tags: Am J Respir Cell Mol Biol Source Type: journals
p38 MAP Kinase Modulates Endotoxin Induced Diaphragm Caspase Activation.
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Conclusions: p38 modulates cytokine induced skeletal muscle caspase activation.
PMID: 19717815 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - August 27, 2009 Category: Molecular Biology Authors: Supinski GS, Callahan LA, Ji X Tags: Am J Respir Cell Mol Biol Source Type: journals
Tissue Factor Pathway Inhibitor Overexpression Inhibits Hypoxia-induced Pulmonary Hypertension.
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Pulmonary hypertension (PH) is a commonly recognized complication of chronic respiratory disease. Enhanced vasoconstriction, pulmonary vascular remodeling and in situ thrombosis contribute to the increased pulmonary vascular resistance observed in PH associated with hypoxic lung disease. The tissue factor pathway regulates fibrin deposition in response to acute and chronic vascular injury. We hypothesized that inhibition of the tissue factor pathway would result in attenuation of pathophysiologic parameters typically associated with hypoxiainduced PH. We tested this hypothesis using a chronic hypoxia-induced murine mod...
Source: American Journal of Respiratory Cell and Molecular Biology - July 30, 2009 Category: Molecular Biology Authors: White TA, Witt TA, Pan S, Mueske CS, Kleppe LS, Holroyd EW, Champion HC, Simari RD Tags: Am J Respir Cell Mol Biol Source Type: journals
Altered Assymetric Dimethyl Arginine Metabolism in Allergically Inflamed Mice Lungs.
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Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), causes uncoupling of NOS leading to generation of reactive nitrogen species such as peroxynitrite. The lung generates a significant amount of ADMA, potentially contributing to plasma ADMA levels that have been related to endothelial dysfunction. ADMA infusion causes increased collagen deposition in lungs, suggesting that it could influence the development of chronic lung diseases such as fibrosis, COPD, and asthma. To explore the link between endogenous ADMA and asthma, we determined the levels of ADMA, enzymes implicated in its...
Source: American Journal of Respiratory Cell and Molecular Biology - July 30, 2009 Category: Molecular Biology Authors: Ahmad T, Mabalirajan U, Ghosh B, Agrawal A Tags: Am J Respir Cell Mol Biol Source Type: journals
Functional Role of TRPC1 and TRPC3 in Normal and Asthmatic Airway Smooth Muscle Cells.
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Conclusions: TRPC3 is an important molecular component of native NSCCs contributing to the resting Vm and [Ca2+]i in normal ASMCs, as well as membrane depolarization and hyperresponsiveness in ovalbumin-sensitized/challenged cells, whereas TRPC1-encoded NSCCs are only activated in ovalbumin-sensitized/challenged airway myocytes.
PMID: 19648473 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - July 30, 2009 Category: Molecular Biology Authors: Xiao JH, Zheng YM, Liao B, Wang YX Tags: Am J Respir Cell Mol Biol Source Type: journals
Limitations of the Murine Nose in the Development of Non-viral Airway Gene Transfer.
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, Stevenson B, Varathalingam A, Siegel C, Scheule RK, Cheng SH, Davies JC, Porteous DJ, Gill DR, Boyd AC, Hyde SC, Alton EW
A clinical programme to assess whether lipid GL67A-mediated gene-transfer can ameliorate cystic fibrosis (CF) lung disease is currently being undertaken by the UKCF Gene Therapy Consortium. We have evaluated GL67A gene transfer to the murine nasal epithelium of wildtype and CF knockout mice to assess this tissue as a test site for gene transfer agents. The plasmids used were regulated by either (a) the commonly used short-acting CMV promoter/enhancer or (b) the ubiquitin-C (UbC) promoter. In a stu...
Source: American Journal of Respiratory Cell and Molecular Biology - July 30, 2009 Category: Molecular Biology Authors: Griesenbach U, Sumner-Jones SG, Holder E, Munkonge FM, Wodehouse T, Smith SN, Wasowicz MY, Pringle I, Casamayor I, Chan M, Coles R, Cornish N, Dewar A, Doherty A, Farley R, Green AM, Jones BL, Larsen MD, Lawton AE, Manvell M, Painter H, Singh C, Somerton Tags: Am J Respir Cell Mol Biol Source Type: journals
Actin Cytoskeleton Regulates Stretch-activated Ca2+ Influx in Human Pulmonary Microvascular Endothelial Cells.
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In conclusion, mechanical stretch activates Ca(2+) influx via stretch-activated channels different from other Ca(2+) influx pathways such as receptor- and store-operated Ca(2+) entries in HPMVECs that is tightly regulated by the actin cytoskeleton. These results suggest that abnormal Ca(2+) homeostasis due to excessive mechanical stretch during mechanical ventilation may play a role in ALI/ARDS progression.
PMID: 19648475 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - July 30, 2009 Category: Molecular Biology Authors: Ito S, Suki B, Kume H, Numaguchi Y, Ishii M, Iwaki M, Kondo M, Naruse K, Hasegawa Y, Sokabe M Tags: Am J Respir Cell Mol Biol Source Type: journals
p70 Ribosomal S6 Kinase is Required for Airway Smooth Muscle Cell Size Enlargement but not Increased Contactile Protein Expression.
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We examined the contribution of p70 ribosomal S6 kinase (p70S6K) to airway smooth muscle hypertrophy, a structural change found in asthma. In human airway smooth muscle cells, transforming growth factor (TGF)-beta, endothelin-1 and cardiotrophin-1 each induced phosphorylation of p70S6K and ribosomal protein S6 while increasing cell size, total protein synthesis and relative protein abundance of alpha-smooth muscle actin and SM22. Transfection of myocytes with siRNA against either p70S6K or S6, or infection with retrovirus encoding a kinase-dead p70S6K, reduced cell size and protein synthesis but had no effect on contractil...
Source: American Journal of Respiratory Cell and Molecular Biology - July 30, 2009 Category: Molecular Biology Authors: Deng H, Hershenson MB, Lei J, Bitar KN, Fingar DC, Solway J, Bentley JK Tags: Am J Respir Cell Mol Biol Source Type: journals
Acid Sphingomyelinase Inhibitors Normalize Pulmonary Ceramide and Inflammation in Cystic Fibrosis.
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Conclusion: These findings employing several structurally different Asm inhibitors identify Asm as primary target in the lung to reduce ceramide concentrations. Inhaling an Asm inhibitor may be a beneficial treatment for CF, with minimal adverse systemic effects.
PMID: 19635928 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - July 26, 2009 Category: Molecular Biology Authors: Becker KA, Riethmüller J, Lüth A, Döring G, Kleuser B, Gulbins E Tags: Am J Respir Cell Mol Biol Source Type: journals
Superoxide Scavengers Improve Rat Pharyngeal Dilator Muscle Performance.
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Conclusions: This study illustrates that superoxide scavengers increase upper airway muscle force and that this effect persists under hypoxic conditions. We conclude that antioxidant treatment may be beneficial as a therapy in obstructive sleep apnoea.
PMID: 19635929 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - July 26, 2009 Category: Molecular Biology Authors: Skelly JR, Bradford A, Jones JF, O'Halloran KD Tags: Am J Respir Cell Mol Biol Source Type: journals
Potential Role of Soluble TRAIL in Epithelial Injury in Children with Severe RSV Infection.
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We report elevated levels of soluble (s)TRAIL released by leukocytes in bronchoalveolar lavage fluid (BALF) of patients with RSV-associated respiratory failure (n=22) as compared to mechanically ventilated patients without pulmonary illness (n=7). Primary bronchial epithelial cells of children without pulmonary disease obtained by non-bronchoscopic cytobrushing expressed both death receptors TRAIL-R1 and -R2, and were found to be susceptible for cell death by human recombinant sTRAIL in vitro. Furthermore, BALF from a RSV patient induced cell death in these cells, which was partly attenuated by inhibiting TRAIL signaling. ...
Source: American Journal of Respiratory Cell and Molecular Biology - July 26, 2009 Category: Molecular Biology Authors: Bem RA, Bos AP, Wösten-van Asperen RM, Bruijn M, Lutter R, Sprick MR, van Woensel JB Tags: Am J Respir Cell Mol Biol Source Type: journals
Sequential Activation of Protein Kinase C Isoforms by Organic Dust is Mediated by Tumor Necrosis Factor.
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Rationale: Dust samples collected from Nebraska swine confinement facilities (hog dust extract, HDE) are known to elicit proinflammatory cytokine release from human bronchial epithelial (HBE) cells in vitro. This response involves the activation of two protein kinase C isoforms (PKCalpha and PKCepsilon). Experiments were designed to investigate the relationship between the two isoenzymes and the degree to which each is responsible for cytokine release in HBE. Experiments also examined the contribution of tumor necrosis factor alpha (TNFalpha) to interleukin (IL)-6 and IL-8 release. Methods: PKCalpha and PKCepsilon acti...
Source: American Journal of Respiratory Cell and Molecular Biology - July 26, 2009 Category: Molecular Biology Authors: Wyatt TA, Slager RE, Heires AJ, Devasure JM, Von Essen SG, Poole JA, Romberger DJ Tags: Am J Respir Cell Mol Biol Source Type: journals
The Urokinase Receptor Supports Tumorigenesis of Human Malignant Pleural Mesothelioma Cells.
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ABSTRACT Malignant pleural mesothelioma (MPM) is a lethal neoplasm for which current therapy is unsatisfactory. The urokinase plasminogen activator receptor (uPAR) is associated with increased virulence of many solid neoplasms but its role in the pathogenesis of MPM is currently unclear. We found that REN human pleural MPM cells expressed 4-10-fold more uPAR than MS-1 or M9K MPM cells or MeT5A human pleural mesothelial cells. In a new orthotopic murine model of MPM, we found that the kinetics of REN cell tumorigenesis is accelerated versus MS-1 or M9K cells, that REN instillates generated larger tumors expressing incre...
Source: American Journal of Respiratory Cell and Molecular Biology - July 26, 2009 Category: Molecular Biology Authors: Tucker TA, Dean C, Komissarov A, Koenig K, Mazar A, Pendurthi U, Allen TC, Idell S Tags: Am J Respir Cell Mol Biol Source Type: journals
IL-13 Regulates Secretion of the TGF-{beta} Superfamily Cytokine Activin A in Allergic Airway Inflammation.
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Activin A is a member of the TGF-beta superfamily and plays a role in allergic inflammation and asthma pathogenesis. Recent evidence suggests that activin A regulates pro-inflammatory cytokine production and is itself regulated by inflammatory mediators. In a murine model of acute allergic airway inflammation, we observed previously that increased activin A concentrations in bronchoalveolar lavage fluid coincide with Th2 cytokine production in lung-draining lymph nodes and pronounced mucus metaplasia in bronchial epithelium. We therefore hypothesised that IL-13, the key cytokine for mucus production, regulates activin ...
Source: American Journal of Respiratory Cell and Molecular Biology - July 26, 2009 Category: Molecular Biology Authors: Hardy CL, Lemasurier JS, Olsson F, Dang T, Yao J, Yang M, Plebanski M, Phillips DJ, Mollard RA, Rolland JM, O'Hehir R Tags: Am J Respir Cell Mol Biol Source Type: journals
Impaired IL-8 Chemokine Secretion by S.aureus-activated Epithelium and T cell Chemotaxis in Cystic Fibrosis.
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This study aims to investigate early S. aureus impact on chemokine secretion by CF epithelial cells and chemotaxis of CF T cells. CF and non-CF AEC were grown in a cell culture model and apically stimulated with S.aureus. Supernatants were quantified for chemokine secretions and assayed for T cell chemotaxis. CF AEC were found to secrete constitutively larger amounts of IL-8, GROalpha, MIG, MIP-3beta and MCP-1 than non-CF epithelial cells. However, S. aureus interaction with epithelial cells increased chemokine production by non-CF cells, whereas it had no effect on CF cells. Interestingly, chemotaxis of T cells derived fr...
Source: American Journal of Respiratory Cell and Molecular Biology - July 12, 2009 Category: Molecular Biology Authors: Al Alam D, Deslee G, Tournois C, Lamkhioued B, Lebargy F, Merten M, Belaaouaj A, Guenounou M, Gangloff SC Tags: Am J Respir Cell Mol Biol Source Type: journals
Transcription Factor GATA-6 is Expressed in Quiescent Myofibroblasts in Idiopathic Pulmonary Fibrosis.
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In conclusion, the hallmark of IPF/UIP histopathology, the fibroblast focus, consists of differentiated, quiescent cells that are prominently expressing GATA-6.
PMID: 19597127 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - July 12, 2009 Category: Molecular Biology Authors: Leppäranta O, Pulkkinen V, Koli K, Vähätalo R, Salmenkivi K, Kinnula VL, Heikinheimo M, Myllärniemi M Tags: Am J Respir Cell Mol Biol Source Type: journals
Oxidative Stress Enhances Toll-like Receptor 3 Response to Double-stranded RNA in Airway Epithelial Cells.
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Virus infections are a major cause of COPD exacerbations. Recently, toll-like receptor 3 (TLR3) has been demonstrated to react to double-stranded RNA (dsRNA) and to be involved in the immune responses after viral infections. In the present study, we examined whether oxidative stress, which is involved in the pathogenesis of COPD, enhances the responses of TLR3 in airway epithelial cells. The effect of hydrogen peroxide (H2O2) on the release of IL-8 from BEAS-2B cells and primary human bronchial epithelial cells after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of viral dsRNA and a...
Source: American Journal of Respiratory Cell and Molecular Biology - July 12, 2009 Category: Molecular Biology Authors: Koarai A, Sugiura H, Yanagisawa S, Ichikawa T, Minakata Y, Matsunaga K, Hirano T, Akamatsu K, Ichinose M Tags: Am J Respir Cell Mol Biol Source Type: journals
Rounding up apoptosis resistance targets in lung cancer.
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PMID: 19525385 [PubMed - indexed for MEDLINE] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - June 28, 2009 Category: Molecular Biology Authors: Powell CA Tags: Am J Respir Cell Mol Biol Source Type: journals
Receptors for Advanced Glycation End-products (RAGE) Targeting Protect against Hyperoxia-Induced Lung Injury in Mice.
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Patients with acute lung injury (ALI) almost always require supplemental oxygen during treatment; however, elevated oxygen itself is toxic. Receptors for advanced glycation end-products (RAGE) are multiligand cell surface receptors predominantly localized to alveolar type I (ATI) cells that influence development and cigarette smoke-induced inflammation, but studies that address the role of RAGE in ALI are insufficient. In the present investigation, we test the hypothesis that RAGE signaling functions in hyperoxia-induced inflammation. RAGE null mice exposed to hyperoxia survived 3 days longer than age-matched wild-type...
Source: American Journal of Respiratory Cell and Molecular Biology - June 24, 2009 Category: Molecular Biology Authors: Reynolds PR, Schmitt RE, Kasteler SD, Sturrock A, Sanders K, Bierhaus A, Nawroth PP, Paine Iii R, Hoidal JR Tags: Am J Respir Cell Mol Biol Source Type: journals
Systemic Administration of Sphingosine-1-phosphate Increases Bronchial Hyper-responsiveness in the Mouse.
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In conclusion our data demonstrate that S1P signalling is involved in the complex pathway underlying airway hyper-responsiveness.
PMID: 19556602 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - June 24, 2009 Category: Molecular Biology Authors: Roviezzo F, D'Agostino B, Brancaleone V, De Gruttola L, Bucci M, De Dominicis G, Orlotti D, D'Aiuto E, De Palma R, Rossi F, Sorrentino R, Cirino G Tags: Am J Respir Cell Mol Biol Source Type: journals
Nitric Oxide-Mediated Bcl-2 Stabilization Potentiates Malignant Transformation of Human Lung Epithelial Cells.
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This study establishes an important in vitro model that facilitates mechanistic studies of Cr(VI)-induced carcinogenesis, and elucidates a novel mechanism that causes apoptosis-resistant malignant transformation of non-tumorigenic lung cells in response to a human carcinogen.
PMID: 19556603 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - June 24, 2009 Category: Molecular Biology Authors: Azad N, Iyer AK, Wang L, Lu Y, Medan D, Castranova V, Rojanasakul Y Tags: Am J Respir Cell Mol Biol Source Type: journals
Gender Differences in Estrogen Receptor Subcellular Location and Activity in Lung Adenocarcinoma Cells.
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We reported that lung adenocarcinoma cell lines from female, but not male, NSCLC patients respond proliferatively and transcriptionally to estradiol (E2), despite equal protein expression of estrogen receptors alpha and beta (ERalpha and ERbeta). To test the hypothesis that nuclear localization of ERalpha corresponds to genomic E2 activity in lung adenocarcinoma cells from females, cell fractionation, immunoblot, and confocal immunohistochemical microscopy were performed. We report for the first time that E2 increases phospho-serine-118-ERalpha (P-ser118-ERalpha ) and cyclin D1 nuclear colocalization in H1793 but not A549 ...
Source: American Journal of Respiratory Cell and Molecular Biology - June 24, 2009 Category: Molecular Biology Authors: Ivanova MM, Mazhawidza W, Dougherty SM, Klinge CM Tags: Am J Respir Cell Mol Biol Source Type: journals
Regulation of Neuregulin 1ss1-Induced MUC5AC and MUC5B Expression in Human Airway Epithelium.
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Excessive mucus production has been linked to many of the pathological features of respiratory diseases including obstruction of the airways, decline in lung function, increased rates of mortality and increased infections. The mucins MUC5AC and MUC5B contribute to the viscoelastic properties of mucus and are found at elevated levels in the airways of individuals with chronic respiratory diseases. The Th2 cell cytokine interleukin-13 (IL-13) is known to regulate MUC5AC expression in goblet cells of the airways, though much less is known about the regulation of MUC5B expression. In a study to further understand the media...
Source: American Journal of Respiratory Cell and Molecular Biology - June 24, 2009 Category: Molecular Biology Authors: Kettle R, Simmons J, Schindler F, Jones P, Dicker T, Dubois G, Giddings J, Van Heeke G, Jones CE Tags: Am J Respir Cell Mol Biol Source Type: journals
Attenuation of Chronic Pulmonary Inflammation in A2B Adenosine Receptor Knockout Mice.
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In conclusion, genetic removal of A2B adenosine receptors in mice leads to inhibition of allergen-induced chronic pulmonary inflammation and airway remodeling. These findings are in agreement with previous pharmacological studies suggesting a deleterious role for A2B receptor signaling in chronic lung inflammation.
PMID: 19556606 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - June 24, 2009 Category: Molecular Biology Authors: Zaynagetdinov R, Ryzhov S, Goldstein AE, Yin H, Novitskiy SV, Goleniewska K, Polosukhin VV, Newcomb DC, Mitchell D, Morschl E, Zhou Y, Blackburn MR, Peebles Jr RS, Biaggioni I, Feoktistov I Tags: Am J Respir Cell Mol Biol Source Type: journals
MicroRNA Expression in Human Airway Smooth Muscle Cells: Role of miR-25 in Regulation of Airway Smooth Muscle Phenotype.
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Mechanisms by which differentiated, contractile smooth muscle cells become proliferative and secretory is one way airway smooth muscle (ASM) cells respond to mechanical and environmental stress and contributes to inflammatory responses in the lung that result in airway disease. Regulation by microRNAs (miRNAs) has emerged as an important post-transcriptional mechanism regulating gene expression that may modulate ASM phenotype but little is known about the expression and functions of miRNA in smooth muscle. In the present studies, we use microarrays to determine if miRNAs in human ASM cells are altered by a pro-inflamma...
Source: American Journal of Respiratory Cell and Molecular Biology - June 17, 2009 Category: Molecular Biology Authors: Kuhn AR, Schlauch K, Lao R, Halayko AJ, Gerthoffer WT, Singer CA Tags: Am J Respir Cell Mol Biol Source Type: journals
Role of the Serotonergic System in Reduced Pulmonary Function Following Exposure to Methamphetamine.
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Although use of methamphetamine (MA) by smoking is the fastest growing method of administration, very limited data are available describing the effects of smoked MA. Using a murine inhalation exposure system, we explored the pulmonary effects of low-dose acute inhalation exposure to MA vapor (smoke). Inhalation of MA vapor resulted in transiently reduced pulmonary function as measured by transpulmonary resistance (RL), dynamic compliance (Cdyn), and whole body plethysmography (WBP) compared to unexposed controls. These changes were associated with an approximately 34% reduction in serotonin (5-HT) metabolism to 5-hydro...
Source: American Journal of Respiratory Cell and Molecular Biology - June 17, 2009 Category: Molecular Biology Authors: Wells SM, Buford MC, Porter VM, Brunell HL, Bunderson-Schelvan M, Nevin AB, Cardozo-Pelaez F, Holian A Tags: Am J Respir Cell Mol Biol Source Type: journals
Conditional Over-expression of Connective Tissue Growth Factor Disrupts Postnatal Lung Development.
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Connective tissue growth factor (CTGF) is a member of an emerging family of immediate-early gene products that coordinates complex biological processes during development, differentiation and tissue repair. Over-expression of CTGF is associated with mechanical ventilation with high tidal volume and oxygen exposure in newborn lungs. However, the role of CTGF in postnatal lung development and remodeling is not well understood. In the present study, a double transgenic mouse model was generated with doxycycline-inducible over-expression of CTGF in respiratory epithelial cells. Over-expression of CTGF from postnatal day 1 ...
Source: American Journal of Respiratory Cell and Molecular Biology - June 17, 2009 Category: Molecular Biology Authors: Wu S, Platteau A, Chen S, McNamara G, Whitsett J, Bancalari E Tags: Am J Respir Cell Mol Biol Source Type: journals
Advances in Mucous Cell Metaplasia: A Plug for Mucus as a Therapeutic Focus in Chronic Airway Disease.
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Mucous cell metaplasia is induced in response to harmful insults and provides front-line protection to clear the airway of toxic substances and cellular debris. In chronic airway diseases mucous metaplasia persists and results in airway obstruction and contributes significantly to morbidity and mortality. Mucus hypersecretion involves increased expression of mucin genes, and increased mucin production and release. The past decade has seen significant advances in our understanding of the molecular mechanisms by which these events occur. Inflammation stimulates EGFR activation and IL-13 to induce both Clara and ciliated ...
Source: American Journal of Respiratory Cell and Molecular Biology - June 10, 2009 Category: Molecular Biology Authors: Curran DR, Cohn L Tags: Am J Respir Cell Mol Biol Source Type: journals
Deletion of Keap1 in the Lung Attenuates Acute Cigarette Smoke-induced Oxidative Stress and Inflammation.
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In conclusion, activating Nrf2 pathways in tissue-specific Keap1 knockout mice represents an important genetic approach against oxidant induced lung damage.
PMID: 19520915 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology)
Source: American Journal of Respiratory Cell and Molecular Biology - June 10, 2009 Category: Molecular Biology Authors: Blake DJ, Singh A, Kombairaju P, Malhotra D, Mariani TJ, Tuder RM, Gabrielson E, Biswal S Tags: Am J Respir Cell Mol Biol Source Type: journals
Characterization of the Epithelial Sodium Channel Delta Subunit in Human Nasal Epithelium.
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The epithelial sodium channel (ENaC) mediates the first step in Na(+) reabsorption in epithelia cells such as kidney, colon, and airways and may consist of four homologous subunits (alpha, beta, gamma, delta). Predominantly, the alpha-subunit is expressed in these epithelia and it usually forms functional channels with the beta- and gamma-subunits. The delta-subunit was first found in human brain and kidney but the expression was also detected in human cell lines of lung, pancreatic and colonic origin. When co-expressed with beta and gamma accessory subunits in heterologous systems the two known isoforms of the delta-E...
Source: American Journal of Respiratory Cell and Molecular Biology - June 10, 2009 Category: Molecular Biology Authors: Bangel-Ruland N, Sobczak K, Christmann T, Kentrup D, Langhorst H, Kusche-Vihrog K, Weber WM Tags: Am J Respir Cell Mol Biol Source Type: journals
Phosphatidylinositol-3-Kinase/Akt Regulates Bleomycin-Induced Fibroblast Proliferation and Collagen Production.
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Abnormal repair and dysregulated angiogenesis have been implicated in the pathogenesis of pulmonary fibrosis but the underlying mechanisms of regulation are not well understood. The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts and its regulation by reactive oxygen species (ROS). Exposure of lung fibroblasts to bleomycin, a known inducer of fibrosis, resulted in rapid activation of PI3K/Akt and a parallel increase in fibroblast proliferation and collagen production, characteristics of lung fibrosis. Bleomycin had no significant effect on total ...
Source: American Journal of Respiratory Cell and Molecular Biology - June 10, 2009 Category: Molecular Biology Authors: Lu Y, Azad N, Wang L, Iyer AK, Castranova V, Jiang BH, Rojanasakul Y Tags: Am J Respir Cell Mol Biol Source Type: journals
