Nitric oxide and airway epithelial barrier function: Regulation of tight junction proteins and epithelial permeability
ABSTRACT Acute airway inflammation is associated with enhanced production of nitric oxide (NO) and altered airway epithelial barrier function, suggesting a role of NO or its metabolites in epithelial permeability. While high concentrations of S-nitrosothiols disrupted transepithelial resistance (TER) and increased permeability in 16HBE14o− cells, no significant barrier disruption was observed by NONOates, in spite of altered distribution and expression of some TJ proteins. Barrier disruption of mouse tracheal epithelial (MTE) cell monolayers in response to inflammatory cytokines was independent of NOS2, based on similar effects in MTE cells from NOS2−/− mice and a lack of effect of the NOS2-inhibitor 1400W. Cell pre-incubation with LPS protected MTE cells from TER loss and increased permeability by H2O2, which was independent of NOS2. However, NOS2 was found to contribute to epithelial wound repair and TER recovery after mechanical injury. Overall, our results demonstrate that epithelial NOS2 is not responsible for epithelial barrier dysfunction during inflammation, but may contribute to restoration of epithelial integrity.
- SourceAvailable from: Karolyn Godburn
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- "A human bronchial epithelial cell line (HBE) was kindly provided by Dr. Albert van der Vliet-University of Vermont, and cultured as described previously [22,23] and primary human nasal epithelial cells were cultured as described previously . Human cell lines were exposed to either PBS or 25 μg/ml of HDM (Greer, Lenoir, NC). "
ABSTRACT: The endoplasmic reticulum (ER) stress response participates in many chronic inflammatory and autoimmune diseases. In the current study, we sought to examine the contribution of ER stress transducers in the pathogenesis of three principal facets of allergic asthma: inflammation, airway fibrosis, and airways hyperresponsiveness. House Dust Mite (HDM) was used as an allergen for in vitro and in vivo challenge of primary human and murine airway epithelial cells. ER stress transducers were modulated using specific small interfering RNAs (siRNAs) in vivo. Inflammation, airway remodeling, and hyperresponsiveness were measured by total bronchoalveolar lavage (BAL) cell counts, determination of collagen, and methacholine responsiveness in mice, respectively. Challenge of human bronchiolar and nasal epithelial cells with HDM extract induced the ER stress transducer, activating transcription factor 6 alpha (ATF6alpha) as well as protein disulfide isomerase, ERp57, in association with activation of caspase-3. SiRNA-mediated knockdown of ATF6alpha and ERp57 during HDM administration in mice resulted in a decrease in components of HDM-induced ER stress, disulfide mediated oligomerization of Bak, and activation of caspase-3. Furthermore, siRNA-mediated knockdown of ATF6alpha and ERp57 led to decreased inflammation, airway hyperresponsiveness and airway fibrosis. Collectively, our work indicates that HDM induces ER stress in airway epithelial cells and that ATF6alpha and ERp57 play a significant role in the development of cardinal features of allergic airways disease. Inhibition of ER stress responses may provide a potential therapeutic avenue in chronic asthma and sub-epithelial fibrosis associated with loss of lung function.Respiratory research 12/2013; 14(1):141. DOI:10.1186/1465-9921-14-141 · 3.09 Impact Factor
Conference Paper: Performances of closed cycle disk MHD generator with Ar/Cs[Show abstract] [Hide abstract]
ABSTRACT: Recent experimental results of shock-tube driven disk MHD generators with Ar/Cs are reported. Experiments were carried out under various load conditions, two different stagnation pressures and various seed fractions. Under the present experimental conditions, effects of the load resistance at the nozzle on enthalpy extractions were small. Enthalpy extractions remained small for the single load resistance. Effects of the stagnation pressure on enthalpy extractions were also found to be small. By optimizing seed fractions, enthalpy extractions higher than 20% were achieved for the segmented load resistance. About 35-45% of the inlet stagnation pressure was lost, even in the nozzle, by Joule dissipation and differences of the total pressure loss at each load conditions were small. The pressure loss due to the shock wave was found to be small owing to the low incident Mach number of the flow. Different kinds of discharge structures were found. A circular luminous discharge due to shock waves appeared, even in the nozzle, under open circuit nozzle conditions. For a single load resistance, spoke instability appeared in the nozzle, this being due to the low electrical conductivity of the plasma in the nozzleEnergy Conversion Engineering Conference, 1996. IECEC 96. Proceedings of the 31st Intersociety; 09/1996
- Biomedical Engineering Conference, 1998. Proceedings of the 17th Southern; 03/1998