Nitric oxide and airway epithelial barrier function: regulation of tight junction proteins and epithelial permeability.
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.
Olson
Nels
N
Department of Pathology, College of Medicine, University of Vermont, D205 Given Building, 89 Beaumont Avenue, Burlington VT 05405, USA.
Greul
Anne-Katrin
AK
Hristova
Milena
M
Bove
Peter F
PF
Kasahara
David I
DI
van der Vliet
Albert
A
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse