EGCG Regulates Mucin by p38 MAPK/MMP‐9 Pathway in Asthma

Abstract

Objective: Mucus plays an important role in protecting human airways from external environments by entrapping inhaled foreign particles and bacteria, and clearing them from the airways by ciliary movement. Epigallocatechin-3-gallate (EGCG) is a major component of green tea extract and known to provide numerous functions, such as anti-oxidant effect, anti-tumor effect, anti- diabetic effect, and anti-inflammatory effect. However, the precise mechanism of action about anti-inflammatory effect of EGCG is not fully defined. Method: The effect of EGCG on phorbol 12-myrisate 13- acetate (PMA)–induced MUC5B expression and signaling pathways were investigated in human NCI-H292 airway epithelial cells, human nasal epithelial cells, and in asthma model of mice. Results: PMA-induced MUC5B mRNA and protein levels were significantly decreased after treatment with EGCG. PMA increased phosphorylation of p38 MAPK and this was significantly decreased after pretreatment with EGCG. PMA induced MMP-9 overexpression and this was significantly attenuated by pretreatment with EGCG or specific inhibitor for p38 MAPK (SB203580). And EGCG inhibited PMA-induced MMP-9 protein activities in gelatin zymography. PMA induced MMP-9 and MUC5B over-expression in human nasal epithelial cells and this was significantly attenuated by pretreatment with EGCG. Conclusion: The results of this study demonstrated that EGCG down-regulates MUC5B expression through the p38 MAPK dependent MMP-9 signaling pathway. These results suggest that EGCG may have protective effect on asthma through the regulation of mucin gene expression in airway epithelial cells. Furthermore, EGCG could be a novel therapeutic agent for controlling asthma.