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Articles in PresS, published online ahead of print February 6, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00494.2001
Submitted on November 19, 2001
Accepted on January 24, 2002
B and MAP Kinase Pathways in Human Colonic Subepithelial Myofibroblasts
1 Department of Internal Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
* To whom correspondence should be addressed. E-mail: andoh{at}belle.shiga-med.ac.jp.
Colonic subepithelial myofibroblasts (SEMFs) may play a role in the modulation of mucosal inflammatory responses. We investigated the effects of IL-17 on IL-6 and chemokine (IL-8 and MCP-1) secretion in colonic SEMFs. cytokine was determined by ELISA and Northern blotting. NF-B DNA-binding activity was evaluated by EMSAs. The activation of mitogen-activated protein (MAP) kinase was assessed by immunoblotting. IL-6, IL-8 and MCP-1 secretions were rapidly induced by IL-17. IL-17 induced NF-B activation within 45 min after stimulation. A blockade of NF-B activation markedly reduced these responses. MAP kinase inhibitors (SB203580, PD98059 and U0216) significantly reduced the IL-17-induced IL-6 and chemokine secretion. The combination of either IL-17 plus IL-1ß or IL-17 plus TNF-
enhanced cytokine secretion: in particular, the effects of IL-17 plus TNF- on IL-6 secretion were much stronger than the other responses. This was dependent on the enhancement of IL-6 mRNA stability. In conclusion, human SEMFs secreted IL-6, IL-8 and MCP-1 in response to IL-17. These responses might play an important role in the pathogenesis of gut inflammation.
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