| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
The p38 mitogen-activated protein kinase (MAPK) is a stress-activated enzyme responsible for transducing inflammatory signals. On CD8+ T lymphocytes, p38 expression correlates with cytotoxic activity. Concerning apoptotic signaling pathways, p38 is activated by TNF-α and activation of p38 may induce apoptosis. Methods. Heterotopic small bowel transplantation (SBT) was performed. Group1. LEW → LEW (n=3), Group2. BN → LEW (n=5, no treatment), Group3, BN → LEW (n=3, FK506 0.5 mg/kg, i.m.for 7 days). Group4 BN → LEW (n=3, anti-TNF-α antibody ; 1.0mg/kg, i.p.injection at SBT). Histology, apoptosis, immunostaining of p38 and phosphospecific p38, and Western blot of phosphospecific p38 were examined. Results. The histopathologic findings of Group 1 on day 7 after transplantation, moderate to serve rejection was observed in Group 2. On the other hand, Group 3 and 4 on day 7 after transplantation showed mild to moderate rejection. The graft infiltrating CD8a/p38-double positive cells in Group 2 significantly increased compared with Group3. Concerning TUNEL-positive cells 10 HPF by Mann-Whitney U-test, there were more positive cells in Group 2 (9.4±3.6) than in Group 1 (0.7±0.6) (p=0.024). However, the number of positive cells in Group 4 (4.3±1.5) decreased significantly compared with Group 2 (p=0.047). There was no significant difference in the number of cells expressing p38 among four groups. In expression of phosphospecific p38, the numbers of positive cells in Group 2 seemed like more than that in Group 4. In the western blotting of phosphospecific p38 in rejecting allografts, immunoreactive bands in Group 2 were detected stronger than that in Group 4. Conclusions. Since the infiltrating cells at allograft rejection would predominantly express phosphospecific p38, combined FK506 and anti-TNF antibody therapy might success by suppressing the activation of p38.
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