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Background and Objectives:Mucus hypersecretion is a major problem in inflamatory airway disease. Interleukin-1β (β) has been implicated in the pathogenesis of inflammatory airway diseases. This study was designed to investigate the signal transduction mechanism and the relationship between cycloxygenase-2 (COX-2) expression and the IL-1β-mediated MUC5AC secretion. Materials and Method:In cultured human airway NCI-H292 epithelial cells, the IL-1β-mediated MUC5AC gene expression and mucin secretion were analyzed by reverse transcription-polymerase chain reaction and imunoasay. To identify the signal transduction pathway of the IL-1β-mediated MUC5AC expresion, we used specific inhibitors. Results:IL-1β in-duced COX-2 and MUC5AC expresion at the mRNA and protein levels. Mucin secretion was blocked by NS398 and resve-ratrol, selective COX-2 inhibitors. Prostaglandin E2 (PGE2) directly induced MUC5AC expresion at both mRNA and protein levels in a dose-dependent manner. Cells activated by IL-1β showed increased extracellular-regulated protein kinase (ERK) 1/2 β-induced MUC5AC gene expresion and mucin secretion were blocked by PD98059, the MEK/ ERK inhibitor and SB203580, the p38 inhibitor. Furthermore, inhibition of both mitogen-activated protein kinases (MAPKs) reduced the IL-1β-induced COX-2 expresion and PGE2 synthesis. Ro31-8220, the PKC inhibitors prevented the IL-1β-induced COX-2 expresion and mucin secretion. Also Ro31-8220 inhibited the IL-1β-mediated MAPKs phosphorylation. Conclusion:IL-1βp38-COX-2-PGE2 in the human airway NCI-H292 epithelial cels. (Korean J Otolaryngol 203 ;46 :27-34)