Involvement of Epidermal Growth Factor Receptor Signaling into the Regulation of Airway MUC5AC Mucin Production by Tussilagone

Abstract

We investigated whether tussilagone, a natural product isolated from Tussilago farfara, significantly affects the mRNA and protein expression levels of mucin 5AC (MUC5AC) in the airways. The human respiratory epithelial cell line, NCI-H292, was pretreated with tussilagone for 30 min and then treated with epidermal growth factor (EGF) for a further 24 h. MUC5AC protein and mRNA expression levels were measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. To determine the mechanism of action of tussilagone, its effect on the EGF receptor (EGFR) signaling pathway was examined using western blotting analysis. Tussilagone inhibited the EGFinduced protein and mRNA expression of MUC5AC and suppressed the expression and phosphorylation of EGFR. Moreover, tussilagone inhibited the phosphorylation of mitogen-activated protein kinase (MAPK)/extracellular signalregulated kinase 1/2 and p38 MAPK. It also suppressed the nuclear localization of specificity protein-1. These results suggested that tussilagone inhibits the expression of MUC5AC in the airways by affecting the EGFR signaling pathway.