RT Journal Article
SR Electronic
T1 Interleukin-1β Induces MUC2 and MUC5AC Synthesis through Cyclooxygenase-2 in NCI-H292 Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1112
OP 1118
DO 10.1124/mol.62.5.1112
VO 62
IS 5
A1 Kim, Yong-Dae
A1 Kwon, Eun-Jin
A1 Park, Dae-Won
A1 Song, Si-Youn
A1 Yoon, Seok-Keun
A1 Baek, Suk-Hwan
YR 2002
UL http://molpharm.aspetjournals.org/content/62/5/1112.abstract
AB Interleukin-1β (IL-1β) has been implicated in the pathogenesis of inflammatory diseases of the airway. In this study, we investigated the regulation of MUC2 and MUC5AC expression and of their regulatory mechanisms through cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Cells activated by IL-1β showed increased COX-2, MUC2, and MUC5AC expressions at both the mRNA and protein levels. Mucin production was blocked by the selective COX-2 inhibitor NS398, and PGE2 directly induced MUC2 and MUC5AC expression at both the mRNA and protein levels in a dose-dependent manner. These results suggest a role for PGE2 in IL-1β–induced mucin synthesis in NCI-H292 cells. To investigate the roles of molecules upstream of COX-2 in mucin regulation, we examined the role of mitogen-activated protein kinases (MAPKs). Cells activated by IL-1β showed increased extracellular signal-regulated kinase (ERK)1/2 and p38 phosphorylation, and IL-1β–induced MUC2 and MUC5AC production was blocked by the ERK pathway inhibitor PD98059 or the p38 inhibitor SB203580. The inhibition of both MAPKs reduced IL-1β–induced COX-2 expression and PGE2 synthesis. Furthermore, the addition of PGE2 to cells overcame the inhibitory effects of both MAPK inhibitors in IL-1β–induced mucin production. These results indicate that in human pulmonary epithelial cells, IL-1β activates ERK or p38 to induce COX-2 production, which in turn induces MUC2 and MUC5AC production.