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Pathological roles of granulomatous formation and Analysis of correlation with extrathymic T lymphocytes in Endotoxin-induced liver injury.

内毒素性肝损伤中肉芽肿形成的病理作用及其与胸腺外T淋巴细胞的相关性分析。

基本信息

批准号：
11670467
负责人：
MATSUI Kiyoshi
金额：
$ 2.3万
依托单位：
HYOGO COLLEGE OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

P.acnes treatment induces Type-1 T cells in the liver by induction of IL-12 andII-18 production from kupffer cells. It is suggested that Kupffer cells is important roles in this process of granulomatoous formation. For the purpose of analysis of roles of Kupffer cells, we compared cytokine production by kupffer cells between P.acnes treatment and Schistosoma mansoni-soluble worm antigen preparation (SWAP) treatment. Non-treated Kupffer cells produce IL-6, IL-10, IL-12, IL-18, TNF-a by LPS.P.acnes-elicited Kupffer cells prduce IL-12, IL-18, TNF-a, IL-6 and IL-10 by LPS.On the other hand, SWAP-stimulated Kupffer cells produce IL-6, IL-10, IL-12, IL-18 and TNF-a by LPS.Interestingly, they produce IL-4, IL-13, IL-6 and IL-10 by SWAP.It is very unique events of IL-4 production by Kupffer cells from infected mice in respnse to SWAP.Acute graft-versus-host disease (aGVHD), fatal side effects of bone marrow transplantation, has been shown to be accompanied with evevation of serum levels of interleukin (IL)-18. Here, we investigated the mechanism underlying the accumulation of IL-18 in a GVHD in mice. Lethally irradiated recipients transplanted with H-2 disparate donor splenocytes confessed aGVHD and contained markedly elevated serum levels of IL-18. While recipients transplanted with gld/gld spleen cells that lack functional Fasligand (FasL), contained only normal ranges of IL-18, indicating FasL-medicated IL-18 release in aGVHD.The wild type hosts engrafed with caspase-1-deficent cells revealed marked increases of IL-18 level similar to those engrafted with wild type cells, while caspase-1-dependent recipients engrafted with wild type cells showed only slight elevation of serum IL-18, indicating that IL-18 elevation is derived from host cells in a caspase-1-dependent manner. These results suggested FasL-mediated caspase-1-dependent IL-18 secretion in a GVHD in mice.

痤疮丙酸杆菌治疗通过诱导库普弗细胞产生IL-12和II-18来诱导肝脏中的1型T细胞。提示枯否细胞在肉芽肿形成过程中起重要作用。为了分析枯否细胞的作用，我们比较了痤疮丙酸杆菌处理和曼氏血吸虫可溶性蠕虫抗原制剂（SWAP）处理之间枯否细胞产生细胞因子的情况。LPS刺激Kupffer细胞产生IL-6、IL-10、IL-12、IL-18、TNF-α，LPS刺激Kupffer细胞产生IL-4、IL-13、IL-18、TNF-α、IL-6、IL-10，LPS刺激Kupffer细胞产生IL-12、IL-18、TNF-α，LPS刺激Kupffer细胞产生IL-6、IL-10、IL-12、IL-18、TNF-α急性移植物抗宿主病（Acute graft-versus-host disease，aGVHD）是骨髓移植的一种严重副作用，其发生与血清白细胞介素（IL）-18水平升高有关。在这里，我们研究了小鼠GVHD中IL-18积累的机制。致死性照射的受体移植H-2不同的供体脾细胞承认aGVHD，并含有显着升高的血清IL-18水平。而移植缺乏功能性FasL（functional Fasligand）的gld/gld脾细胞的受体仅含有正常范围的IL-18，表明aGVHD中FasL介导的IL-18释放。而植入野生型细胞的半胱天冬酶-1依赖性受体仅显示血清IL-18轻微升高，表明IL-18升高是以半胱天冬酶-1依赖性方式源自宿主细胞。这些结果表明在小鼠GVHD中FasL介导的caspase-1依赖性IL-18分泌。