1999 Fiscal Year Final Research Report Summary
The role of abnormal expression of complement activation-regulatory proteins in the pathogenesis of intestinal mucosal damages
Project/Area Number |
09670541
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Shiga University of Medical Science |
Principal Investigator |
SATOME Takao Shiga University of Medical Science, Assistant Professor, 医学部, 助手 (60311726)
|
Co-Investigator(Kenkyū-buntansha) |
ANDOH Akira Shiga University of Medical Science, Assistant Professor, 医学部, 助手 (90252395)
|
Project Period (FY) |
1997 – 1999
|
Keywords | complement / Inflammatory bowel disease / DAF / butyrate |
Research Abstract |
The secretory IgA system has been established as a potent immunological protection system in the intestinal tract. In addition, we have reported that high amounts of complement proteins are secreted into the intestinal tract from bile and pancreatic juice. Furthermore, we have found that intestinal epithelial cells are local biosynthetic site for complement proteins. Thus, complement system plays an important role in the immunologic protection in the intestinal mucosa. However, complement activation induces the mucosal damages by itself, and intestinal epithelial cells are expressing several complement activation regulatory proteins to protect from complement-mediated cell injury. Decay-accelerating factor (DAF) is one of complement activation regulatory proteins of which expression are induced by TNF-α and IL-4. In this study, we attempted to define the pathogenesis of inflammatory bowel disease in the aspects of the abnormal expression of complement regulatory proteins. Our study for these three years demonstrated several novel findings. At first, DAF expression was increased in the inflamed mucosa of ulcerative colitis (UC) patients. As second, DAF expression is induced by TNF-α and IL-4, but decreased by sodium butyrate. Third, sodium butyrate increased complement C3 secretion in intestinal epithelial cells. From these results, we concluded that butyrate, one of short-chain fatty acids generated by bacterial fermentation, plays an important role in the regulatory mechanisms of complement protein secretion and complement regulatory-protein expression in the intestinal epithelial cells. It is likely that the control of bacterial fermentation may be one of effective therapeutic strategies in the treatment of IBD patients.
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Research Products
(10 results)