| Co-Investigator(Kenkyū-buntansha) |
SEISHIMA Mituru GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (10171315)
MORIWAKI Hisataka GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (50174470)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
It is well known that tumor necrosis factor (TNF) plays a key role in the immunopathogenesis of inflammatory bowel disease (IBD) ; the mechanism, however, has not yet been defined. To elucidate the role of the TNF receptor in IBD, we investigated the effect of administering an enema containing 2,4,6-trinitrobenzene sulphonic acid (TNBS), which produces many histological and immunological conditions similar to those of Crohn's disease, using wild (WT), TNFR-1KO, TNFR-2KO and TNFR-1,2KO C57BL/6 strain mice. Mice were irrigated with 6 mg of TNBS into the colon via the anus and sacrificed one week later. In the histological assessment, inflammatory cell scores showed no significant differences among all TNBS-administered groups, whereas tissue damage scores were significantly lower in TNFR-1KO and TNFR-1,2KO mice than in WT mice. The apoptotic indexes of mononuclear cells in the lamina propria of all TNBS-administered groups assessed by TUNEL straining were significantly lower than that of controls. Serum TNF levels of all TNBS-administered groups did not differ significantly from that of, controls, whereas TNF-a mRNA expression in the colon was significantly higher in all TNBS-administered groups than in controls. Further, NF-kb activities were enhanced in WT and TNFR-2KO mice compared with those in control mice. In conclusion, the present data suggest that continuous infiltration of inflammatory cells is substantially responsible for the pathogenesis of TNBS-colitis in mice, which is closely associated with defective apoptosis of mononuclear cells in the lamina propria but not with the TNF/TNFR signaling system.
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