Korean J Otolaryngol-Head Neck Surg.  2000 Jul;43(7):719-723.

The Role of p38 MAP Kinase Signal Transduction in the Induction of MUC 8 Gene Expression in Normal Human Nasal Epithelial Cells

• Yoon JH
• Lee WJ

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.

Keyword

Airway epithelial cells; p38 MAP kinase; MUC 8; Signal transduction

MeSH Terms

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
Antibodies
Mucins
Phosphotransferases
RNA, Messenger
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases