Mucus hypersecretion is a clinically important manifestation of chronic inflammatory airway diseases, such as
asthma and
Chronic obstructive pulmonary disease (
COPD).
Mucin production in airway epithelia is increased under conditions of oxidative stress. Src homology 2 domain-containing
protein tyrosine phosphatase (SHP)-1 suppression is related to the development of airway
inflammation and increased ROS levels. In this study, we investigated the role of SHP-1 in
mucin secretion triggered by oxidative stress. Human lung mucoepidermoid H292
carcinoma cells were transfected with specific
siRNA to eliminate SHP-1 gene expression. Cultured cells were treated with
hydrogen peroxide (H(2)O(2)), and
Mucin 5AC(MUC5AC) gene expression and
mucin production were determined. Activation of
p38 mitogen activated protein kinase (MAPK) in association with MUC5AC production was evaluated.
N-acetylcysteine (NAC) was employed to determine whether
antioxidants could block MUC5AC production. To establish the precise role of p38,
mucin expression was observed after pre-treatment of SHP-1-depleted H292 cells with the p38 chemical blocker. We investigated the in vivo effects of oxidative stress on airway mucus production in SHP-1-deficient heterozygous (mev/+) mice. MUC5AC expression was enhanced in SHP-1 knockdown H292 cells exposed to H(2)O(2), compared to that in control cells. The ratio between phosphorylated and total p38 was significantly increased in SHP-1-deficient cells under oxidative stress. Pre-treatment with NAC suppressed both MUC5AC production and p38 activation. Blockage of
p38 MAPK led to suppression of MUC5AC
mRNA expression. Notably,
mucin production was enhanced in the airway epithelia of mev/+ mice exposed to oxidative stress. Our results clearly indicate that SHP-1 plays an important role in airway
mucin production through regulating oxidative stress.