| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Research Abstract |
Colonic subepithelial myofibroblasts (SEMFs) may play a role in the modulation of mucosal inflammatory responses via the secretion of several pro-inflammatory cytokines. We investigated the effects of interleukin (IL)-17 on IL-6 and chemokine [IL-8 and monocyte chemoattractant protein (MCP)-1] secretion in colonic SEMFs. IL-6, IL-8 and MCP-1 secretion was rapidly induced by IL-17. EMSAs demonstrated that the addition of IL-17 induced NF-kB activation within 1.5 h after stimulation, and a blockade of NF-kB activation by PDTC and TPCK markedly reduced the IL-17-induced IL-6, IL-8 and MCP-1 mRNA expression. IL-17 induced a rapid activation of ERK p42/44 and p38 MAP kinases, and MAP kinase inhibitors (SB202190, PD98059 and U0216) significantly reduced IL-17-induced IL-6, IL-8 and MCP-1 secretion. The combination of either IL-17 plus IL-1β or IL-17 plus TNF-α enhanced IL-6, IL-8 and MCP-1 secretion : in particular, the effects of IL-17 plus TNF-α on IL-6 secretion were much stronger than other responses. This was dependent on the modulation of IL-6 mRNA stability. In conclusion, human SEMFs secreted a large amount of IL-6, IL-8 and MCP-1 in response to IL-17. These responses might play an important role in the pathogenesis of inflammatory bowel disease. We evaluated changes in IL-17 expression in the inflamed mucosa and in the serum of IBD patients. The average number of IL-17+ cells was significantly increased in active UC and CD patients compared to inactive patients. IL-17 mRNA expression was not detected in normal mucosa, but was detectable in the mucosa from active UC and CD patients. IL-17 expression in the mucosa and serum was increased in IBD patients. It is likely that IL-17 expression in IBD patients may be associated with the altered immune and inflammatory responses in the intestinal mucosa.
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