Effect of fudosteine on mucin production.
Fudosteine is a novel mucoactive agent, although little is known about how fudosteine decreases mucin production. The present study examined the effects of fudosteine on MUC5AC mucin synthesis and cellular signalling. An animal model of lipopolysaccharide (LPS)-induced inflammation and a bronchial epithelial cell line model of tumour necrosis factor (TNF)-alpha-induced inflammation were used. Fudosteine was administered before stimulation with LPS or TNF-alpha. 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-alpha in NCI-H292 cells; these effects were inhibited by fudosteine treatment. After stimulation with LPS or TNF-alpha, 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. The present results suggest fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of extracellular signal-related kinase and p38 mitogen-activated protein kinase in vivo and extracellular signal-related kinase in vitro.
Rhee
C K
CK
Dept of Internal Medicine, St Mary's Hospital, The Catholic University Medical College, #62 Yeoi-Do Dong, Young Dung Po Gu, Seoul, Korea.
Kang
C M
CM
You
M B
MB
Yoon
H K
HK
Kim
Y K
YK
Kim
K H
KH
Moon
H S
HS
Park
S H
SH
Song
J S
JS
D000818:Animals; D045744:Cell Line, Tumor; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D055271:Mucin 5AC / Q000096:biosynthesis / Q000737:chemistry*; D009077:Mucins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha; D003553:Cystine; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; C113797:fudosteine