J Korean Med Sci.
2002 Dec;17(6):765-771. 10.3346/jkms.2002.17.6.765.
Interleukin-1 beta Induces MUC2 Gene Expression and Mucin Secretion via Activation of PKC-MEK/ERK,and PI3K in Human Airway Epithelial Cells
- Affiliations
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- 1Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Korea. ydkim@med.yu.ac.kr
- 2Department of Thoracic and Cardiovascular Surgery, College of Medicine, Yeungnam University, Daegu, Korea.
- 3Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Korea.
- 4Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea.
- KMID: 648785
- DOI: http://doi.org/10.3346/jkms.2002.17.6.765
Abstract
- Interleukin 1 beta (IL-1 beta), a proinflammatory cytokine, is related with inflammatory diseases and it up-regulates MUC2 gene expression and mucin secretion. This study was designed to investigate the signal transduction pathway of the IL-1 beta-mediated MUC2 gene expression and mucin secretion in human airway epithelial cells. In cultured human airway NCI-H292 epithelial cells, the steady state of the mRNA level of MUC2 gene expression and mucin secretion induced by IL-1 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme immunoassay, and immunoblot analysis. To observe the signal pathway of the IL-1 beta-mediated MUC2 gene expression and mucin secretion, we used several specific inhibitors. PD98059 (MEK/ERK inhibitor) suppressed IL-1 beta-mediated MUC2 gene expression and mucin secretion, while SB203580 (p38 inhibitor) did not. Ro31-8220 (PKC inhibitor) inhibited IL-1 beta-mediated MUC2 gene expression and mucin secretion. It inhibited ERK phosphorylation, but did not inhibit p38 phosphorylation. LY294002 (PI3K inhibitor) also suppressed MUC2 expression, but did not inhibit any MAPKs phosphorylation. These results suggest that the IL-1 -mediated MUC2 gene expression and mucin secretion in NCI-H292 cells are regulated through activation of the PKC-MEK/ERK pathway, and that PI3K is also involved in the IL-1 beta-mediated MUC2 gene expression and mucin secretion.
Keyword
MeSH Terms
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1-Phosphatidylinositol 3-Kinase/*metabolism
Cell Line
Chromones/pharmacology
Dose-Response Relationship, Drug
Enzyme Activation
Enzyme Inhibitors/pharmacology
Epithelium/*enzymology
Flavonoids/pharmacology
Humans
Imidazoles/pharmacology
Immunoassay
Immunoblotting
Indoles/pharmacology
Interleukin-1/metabolism/*physiology
Lung/cytology/*metabolism
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases/*metabolism
Morpholines/pharmacology
Mucin-2
Mucins/*biosynthesis/metabolism
Phosphorylation
Protein Kinase C/*metabolism
Protein Structure, Tertiary
Pyridines/pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Time Factors
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