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Cathelicidin stimulates colonic mucus synthesis by up‐regulating MUC1 and MUC2 expression through a mitogen‐activated protein kinase pathway
Author(s) -
Tai Emily K.K.,
Wong Helen P.S.,
Lam Emily K.Y.,
Wu William K.K.,
Yu L.,
Koo Marcel W.L.,
Cho C.H.
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21615
Subject(s) - cathelicidin , mucus , mucin , muc1 , protein kinase a , kinase , small interfering rna , phosphorylation , biology , p38 mitogen activated protein kinases , microbiology and biotechnology , chemistry , biochemistry , peptide , antimicrobial peptides , transfection , ecology , gene
Mucus forms the physical barrier along the gastrointestinal tract. It plays an important role to prevent mucosal damage and inflammation. Our animal study showed that antibacterial peptide ‘cathelicidin’ increased mucus thickness and prevented inflammation in the colon. In the current study, we examined the direct effect and mechanisms by which the peptide increased mucus synthesis in a human colonic cell line (HT‐29). Human cathelicidin (LL‐37) dose‐dependently (10–40 µg/ml) and significantly stimulated mucus synthesis by increasing the D ‐[6‐ 3 H] glucosamine incorporation in the cells. Real‐time PCR data showed that addition of LL‐37 induced more than 50% increase in MUC1 and MUC2 mRNA levels. Treatment with MUC1 and MUC2 siRNAs normalized the stimulatory action of LL‐37 on mucus synthesis. LL‐37 also activated the phosphorylation of mitogen‐activated protein (MAP) kinase in the cells. A specific inhibitor of the MAP kinase pathway, U0126, completely blocked the increase of MUC1 and MUC2 expression as well as mucus synthesis by LL‐37. Taken together, LL‐37 can directly stimulate mucus synthesis through activation of MUC1 and MUC2 expression and MAP kinase pathway in human colonic cells. J. Cell. Biochem. 104: 251–258, 2008. © 2007 Wiley‐Liss, Inc.