Epigallocatechin-3-gallate inhibits interleukin-1beta-induced MUC5AC gene expression and MUC5AC secretion in normal human nasal epithelial cells.
It has been reported that the proinflammatory cytokine interleukin-1beta (IL-1beta) induces mucus hypersecretion in normal human nasal epithelial (NHNE) cells and that the MAP kinase pathway may be an important signal pathway in IL-1beta-induced MUC5AC gene expression. Green tea (Camellia sinensis) polyphenols are potent anti-inflammatory agents and have been shown to inhibit inflammation in tumor cell lines and cultured respiratory epithelial cells. In this study, we examined the effect of (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on IL-1beta-induced MUC5AC gene expression and secretion in NHNE cells. After cells had been treated with IL-1beta (10 ng/ml) and pretreated with EGCG (10, 50 and 100 microM), mRNA expression of MUC5AC was determined by real-time polymerase chain reaction. The suppression of each signal pathway protein was determined by Western blot analysis after treatment with IL-1beta and EGCG, respectively. IL-1beta increased MUC5AC gene expression and MUC5AC secretion. EGCG markedly suppressed IL-1beta-induced MUC5AC gene expression and MUC5AC secretion via suppression of the phosphorylation of ERK MAP kinase, MSK1, and transcription factor, cAMP response element-binding protein. IL-1beta increased the number of cells staining positive with MUC5AC antibodies, and EGCG treatment decreased this number. Our data suggest that EGCG may be an effective inhibitor of IL-1beta-induced mucus hypersecretion.
D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008175:Lung Neoplasms; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D055271:Mucin 5AC; D009077:Mucins / Q000235:genetics* / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D053583:Interleukin-1beta; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D002392:Catechin; C045651:epigallocatechin gallate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3