Korean J Otolaryngol-Head Neck Surg.  2003 Jan;46(1):27-34.

Interleukin-1beta-Mediated MUC5AC Gene Expression and Mucin Secretion via PKC-ERK/p38-COX-2-PGE2 in Human Airway Epithelial Cells

• Kim YD
• Bai CH
• Woo HJ

Abstract

BACKGROUND AND OBJECTIVES
Mucus hypersecretion is a major problem in inflammatory airway disease. Interleukin-1beta (IL-1beta) has been implicated in the pathogenesis of inflammatory airway diseases. This study was designed to investigate the signal transduction mechanism and the relationship between cyclooxygenase-2 (COX-2) expression and the IL-1beta-mediated MUC5AC secretion. MATERIALS AND METHOD: In cultured human airway NCI-H292 epithelial cells, the IL-1beta-mediated MUC5AC gene expression and mucin secretion were analyzed by reverse transcription-polymerase chain reaction and immunoassay. To identify the signal transduction pathway of the IL-1beta-mediated MUC5AC expression, we used specific inhibitors. RESULTS: IL-1beta induced COX-2 and MUC5AC expression at the mRNA and protein levels. Mucin secretion was blocked by NS398 and resveratrol, selective COX-2 inhibitors. Prostaglandin E2 (PGE2) directly induced MUC5AC expression at both mRNA and protein levels in a dose-dependent manner. Cells activated by IL-1beta showed increased extracellular-regulated protein kinase (ERK) 1/2 and p38 phosphorylation. IL-1beta-induced MUC5AC gene expression 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-1beta-induced COX-2 expression and PGE2 synthesis. Ro31-8220, the PKC inhibitors prevented the IL-1beta-induced COX-2 expression and mucin secretion. Also Ro31-8220 inhibited the IL-1beta-mediated MAPKs phosphorylation. CONCLUSION: IL-1beta-induced MUC5AC gene expression and mucin secretion are regulated through the sequential activation of PKC-ERK/ p38-COX-2-PGE2 in the human airway NCI-H292 epithelial cells.

Keyword

Interleukin-1; MUC5AC; Protein kinase C; Mitogen-activated protein kinase; Cyclooxygenase

MeSH Terms

Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Dinoprostone
Epithelial Cells*
Gene Expression*
Humans*
Immunoassay
Interleukin-1
Interleukin-1beta
Mitogen-Activated Protein Kinases
Mucins*
Mucus
Phosphorylation
Prostaglandin-Endoperoxide Synthases
Protein Kinase C
Protein Kinases
RNA, Messenger
Signal Transduction
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Dinoprostone
Interleukin-1
Interleukin-1beta
Mitogen-Activated Protein Kinases
Mucins
Prostaglandin-Endoperoxide Synthases
Protein Kinase C
Protein Kinases
RNA, Messenger