Abstract |
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 microg/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.
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Authors | Emily K K Tai, Helen P S Wong, Emily K Y Lam, William K K Wu, L Yu, Marcel W L Koo, C H Cho |
Journal | Journal of cellular biochemistry
(J Cell Biochem)
Vol. 104
Issue 1
Pg. 251-8
(May 01 2008)
ISSN: 1097-4644 [Electronic] United States |
PMID | 18059019
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimicrobial Cationic Peptides
- MUC1 protein, human
- MUC2 protein, human
- Mucin-1
- Mucin-2
- Mucins
- RNA, Small Interfering
- Mitogen-Activated Protein Kinases
- Cathelicidins
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Topics |
- Antimicrobial Cationic Peptides
(pharmacology)
- Cell Line
- Colon
(cytology, metabolism)
- Humans
- Mitogen-Activated Protein Kinases
(metabolism)
- Mucin-1
(genetics)
- Mucin-2
- Mucins
(genetics)
- Mucus
(metabolism)
- RNA, Small Interfering
(pharmacology)
- Signal Transduction
- Up-Regulation
(genetics)
- Cathelicidins
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