REJECTION MECHANISM AND IMMUNOSUPPRESSIVE STRATEGY OF SMALL BOWEL TRANSPLANTATION.
REJECTION MECHANISM AND IMMUNOSUPPRESSIVE STRATEGY OF SMALL BOWEL TRANSPLANTATION.
批准号:
09671835
负责人:
KANEHIRO Hiromichi
金额:
$1.6万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 1999
中文摘要
p38丝裂原活化蛋白激酶(MAPK)是一种负责转导炎症信号的应激活化酶。在CD 8 + T淋巴细胞上,p38表达与细胞毒活性相关。关于凋亡信号通路,p38被TNF-α激活,并且p38的激活可诱导凋亡。方法.行异位小肠移植(SBT)。第1组。LEW → LEW(n=3),组2。BN → LEW(n=5,未处理),组3,BN → LEW(n=3,FK 506 0.5 mg/kg,肌肉注射,连续7天)。4组BN → LEW(n=3,抗TNF-α抗体,1.0mg/kg,SBT时腹腔注射)。组织学、细胞凋亡、p38和磷酸化p38的免疫染色以及磷酸化p38的Western blot检测。结果移植后第7天,第1组的组织病理学结果显示,第2组出现中度至重度排斥反应。另一方面,第3组和第4组在移植后第7天表现出轻度至中度排斥反应。第2组移植物浸润的CD 8a/p38双阳性细胞较第3组显著增加。关于通过Mann-Whitney U检验的TUNEL阳性细胞10 HPF,第2组(9.4±3.6)中的阳性细胞多于第1组(0.7±0.6)(p=0.024)。然而,与第2组相比,第4组中的阳性细胞数量(4.3±1.5)显著减少(p=0.047)。四组间p38表达细胞数无显著性差异。磷酸化特异性p38蛋白的表达,第2组阳性细胞数多于第4组。在排斥移植物中磷酸化特异性p38的免疫印迹中,组2中检测到的免疫反应条带强于组4。结论.由于在同种异体移植排斥反应中浸润细胞主要表达磷酸化特异性p38,FK 506和抗TNF抗体联合治疗可能通过抑制p38的活化而成功。
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
New transplantation strategy of gut like organ differentiation from pluripotent stem cells by tissue engineering
-
批准号:24592699
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$3.49万
-
财政年份:2012
-
负责人:KANEHIRO Hiromichi
-
依托单位:
New treatment strategy for Hirschsprung's disease with neural crest stem cells by tissue-engneering
-
批准号:21592280
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.91万
-
财政年份:2009
-
负责人:KANEHIRO Hiromichi
-
依托单位:
Mechanism of graft injury and regeneration in small bowel transplantation
-
批准号:19592065
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.66万
-
财政年份:2007
-
负责人:KANEHIRO Hiromichi
-
依托单位:
THERAPEUTIC POTENTIAL OF TARGETING ANIGIOGENESIS IN CHRONIC REJECTION AND ISCHEMIA-REPERFUSION INJURY IN SMALL BOWEL TRANSPLANTATION
-
批准号:17591867
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$1.86万
-
财政年份:2005
-
负责人:KANEHIRO Hiromichi
-
依托单位:
ROLE OF ANGIOGENESIS AND POTENTIAL OF ANTIANGIOGENESIS AS POSTTRANPLANT TREATMENT IN SMALL BOWEL TRANSPLANTATION
-
批准号:15591891
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$2.24万
-
财政年份:2003
-
负责人:KANEHIRO Hiromichi
-
依托单位:
TORELANCE INDUCTION AND IMMUNOSUPPRESSIVE STERATEGY OF SMALL BOWEL TRANSPLANTATION.
-
批准号:12671741
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$1.92万
-
财政年份:2000
-
负责人:KANEHIRO Hiromichi
-
依托单位:
MECHANISM OF TRANSPLANT CHIMERISM AND SIGNIFICANCE OF MIGRATION OF DONOR-DERIVED CELLS IN ORGAN
-
批准号:05671020
-
项目类别:Grant-in-Aid for General Scientific Research (C)
-
资助金额:$1.41万
-
财政年份:1993
-
负责人:KANEHIRO Hiromichi
-
依托单位:
海外基金