Nitric oxide and airway epithelial barrier function: Regulation of tight junction proteins and epithelial permeability

Department of Pathology, College of Medicine, University of Vermont, D205 Given Building, 89 Beaumont Avenue, Burlington VT 05405, USA
Archives of Biochemistry and Biophysics (Impact Factor: 3.02). 04/2009; 484(2):205-213. DOI: 10.1016/


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.

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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 [24]. Human cell lines were exposed to either PBS or 25 μg/ml of HDM (Greer, Lenoir, NC). "
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