The Role of p38 MAP Kinase Signal Transduction in the Induction of MUC 8 Gene Expression in Normal Human Nasal Epithelial Cells.
- Author:
Joo Heon YOON
1
;
Won Jae LEE
Author Information
1. Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea. wjlee1@yumc.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Airway epithelial cells;
p38 MAP kinase;
MUC 8;
Signal transduction
- MeSH:
Antibodies;
Asthma;
Blotting, Western;
Bronchitis, Chronic;
Cystic Fibrosis;
Epithelial Cells*;
Gene Expression*;
Humans*;
Mucins;
Mucus;
p38 Mitogen-Activated Protein Kinases*;
Phosphotransferases;
RNA, Messenger;
Signal Transduction*;
Tumor Necrosis Factor-alpha;
Up-Regulation
- From:Korean Journal of Otolaryngology - Head and Neck Surgery
2000;43(7):719-723
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND AND OBJECTIVES: In cystic fibrosis, chronic bronchitis, and asthma, the mucociliary mechanism is impaired when mucin is produced excessively. The mRNA encoding MUC8 has been shown to be the major up-regulated mucin under inflammatory condition and is likely to contribute to the airway mucus plugging characteristic of these diseases. The aim of this study is to determine the intracellular signaling pathway directly involved in the MUC8 regulation following inflammatory mediator treatments. MATERIALS AND METHOD: Passage-2 normal human airway epithelial cells were used in all experiments. Inflammatory signal-induced MAP kinase activity was measured by Western blot analysis using phosphospecific anti-active MAP kinase antibodies. Inflammatory signal-induced MUC8 expression was measured in the absence or presence of SB203580 by the semi-quantative RT-PCR. RESULTS: Inflammatory stimuli such as LPS, TNF-alpha, and IL-lbeta activated the p38 MAP kinase and subsequently up-regulated the MUC8 expression. Interestingly, the TNF-alpha or IL-lbeta-inducibility of the MUC8 gene expression was greatly enhanced by specific inhibition of the p38 MAP kinase by using SB 203580 CONCLUSION: These results suggest that the intracellular p38 MAP kinase activity is a negative regulator for the MUC8 up-regulation in human nasal epithelial cells following infiammatory stimuli.
