Interleukin-1beta-Mediated MUC5AC Gene Expression and Mucin Secretion via PKC-ERK/p38-COX-2-PGE2 in Human Airway Epithelial Cells.
- Author:
Yong Dae KIM
1
;
Chang Hoon BAI
;
Hyun Jae WOO
Author Information
1. Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Korea.
- Publication Type:Original Article
- Keywords:
Interleukin-1;
MUC5AC;
Protein kinase C;
Mitogen-activated protein kinase;
Cyclooxygenase
- MeSH:
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
- From:Korean Journal of Otolaryngology - Head and Neck Surgery
2003;46(1):27-34
- CountryRepublic of Korea
- Language:Korean
-
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.
