Effect of fudosteine on mucin production

¹ Dept of Internal Medicine, St Mary's Hospital, The Catholic University Medical College. #62, Yeoi-Do Dong, Young Dung Po Gu, Seoul, Korea

^* To whom correspondence should be addressed. E-mail: Jeong.

	Abstract

Fudosteine is a novel mucoactive agent, although little is known about how fudosteine decreases mucin production. In this study, we examined the effects of fudosteine on MUC5AC mucin synthesis and cellular signaling.

We used an animal model of lipopolysaccharide (LPS) induced inflammation and a bronchial epithelial cell line model of tumour necrosis factor (TNF)- induced inflammation. Fudosteine was administered before stimulation with LPS or TNF-. The MUC5AC mucin levels were assayed, and the expression of the MUC5AC gene was measured. Western blotting was carried out for the detection of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK), and phosphorylated extracellular signal-related kinase (p-ERK).

MUC5AC mucin synthesis and the expression of the MUC5AC gene were increased by LPS in rats or TNF- in NCI-H292 cells, and these effects were inhibited by fudosteine treatment. After stimulation with LPS or TNF-, the expression of p-EGFR, p-p38 MAPK, and p-ERK were detected. Fudosteine treatment reduced the expression levels of p-p38 MAPK and p-ERK in vivo and of p-ERK in vitro.

These results suggest fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of ERK and p38 MAPK in vivo and ERK in vitro.