Cigarette smoke augments XXXX production via the @entity6800 - @entity470 pathway in airway epithelial cells.

@entity1 @entity6800 @entity14018 @entity470 @entity3963 @entity898 @entity1800 @entity5089 @entity1030 @entity1981
BACKGROUND: @entity1800 are a major cause of @entity1030 ( @entity1030 ) exacerbations. @entity6800 ( @entity6800 ) reacts with double-stranded RNA (dsRNA) and participates in the immune response after @entity1800 . In the present study, we examined whether cigarette smoke, which is involved in the pathogenesis of @entity1030 , enhances mucin production via the @entity470 ( @entity470 ) pathway in airway epithelial cells. METHODS: We studied the effects of @entity1981 ( @entity1981 ) on signal transduction and the production of @entity5089 ( @entity5089 ) in NCI-H292 cells and differentiated primary @entity1 bronchial epithelial cells stimulated with a synthetic dsRNA analogue, @entity14018 [ @entity14018 ], used as a @entity6800 ligand. RESULTS: @entity1981 significantly potentiated the production of @entity5089 in epithelial cells stimulated with poly(I:C). Antibodies to @entity470 or @entity470 ligands inhibited @entity1981 -augmented @entity5089 release in poly(I:C)-treated cells. Treatment with poly(I:C) or @entity1981 alone increased the phosphorylation of @entity470 and @entity3963 ( @entity3963 ). However, after poly(I:C) stimulation, @entity1981 did not enhance @entity470 phosphorylation, but did augment @entity3963 phosphorylation. @entity470 inhibitors and an @entity3963 inhibitor inhibited the augmented release of @entity5089 . In addition, treatment with @entity898 , an antioxidant, inhibited the @entity1981 -augmented phosphorylation of @entity3963 and @entity5089 . CONCLUSIONS: These data show that cigarette smoke increases @entity6800 -stimulated @entity5089 production in airway epithelial cells, mainly via @entity3963 signaling. The effect might be mediated in part by oxidative stress. Modulation of this pathway might be a therapeutic target for viral-induced mucin overproduction in @entity1030 exacerbation.
