| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Colonic epithelial cells of patients with ulcerative colitis (UC) express decay-accelerating factor (DAF) in relation to the severity of mucosal inflammation, In this study, we determined whether this factor in stool could be used as a marker of the disease activity in UC patients. Stool DAF was measured by use of an immunoassay in 181stool specimens obtained from 55 patients with UC of various levels of disease activity. Stool DAF concentrations in patients whose UC was were significantly higher than concentrations in patients whose disease was inactive. Values in active UC patients also were higher than those in control patients with diarrhea and in control subjects without apparent colorectal disease. The elevated levels of stool DAF obtained from UC patients in relapse declined markedly in specimens collected after the disease went into remission following medical therapy. Stool DAF levels correlated with the severity of endoscopic and histologic findings and the degree of DAF expr
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ession on the colonic epithelia, These results suggest that the measurement of stool DAF is useful as a non-invasive means of monitoring intestinal disease activity in patients with UC
Cytokines are known to modulate DAF expression in various human cells, and lesions of ulcerative colitis reveal altered profiles of cytokine production. Thus, we evaluated the effects of various cytokines, IL-beta, IL-2, IL-4, IL-6, IL-8, IL-10, and IFN-gamma, on the synthesis and kinetics of DAF protein in HT-29 human intestinal epithelial cells. Using flow cytometry and an enzyme-linked immunosorbent assay, we found that HT-29 cells constitutively express DAF on the cell-surface and spontaneously release DAF into the culture supernatant under standard culture conditions. When the culture supernatant was centrifuged at 100,000 g, nearly a half of DAF was precipitated, indicating that one half of the released DAF was present as a membrane bound form and the other half as a soluble form, Analysis of the culture supernatant of biotin surface-labeled HT-29 cells suggested that the soluble form DAF was derived by secretion from within the cell or by cleavage from the cell surface, Among the cytokines, IL-4 markedly, and IL-beta moderately, enhanced the release of DAF.Actinomycin D, cycloheximide and brefeldin A inhibited the increase in DAF release induced by IL-4 and IL-beta stimulation, These results suggest that DAF is released from intestinal epithelial cells in response to cytokine stimulation and that IL-4 and IL-beta are possible cytokines involved in the DAF release into the colonic lumen of patients with ulcerative colitis. Less
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