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

痤疮治疗通过诱导kupffer细胞产生IL-12和dii -18来诱导肝脏中的1型T细胞。提示库普弗细胞在肉芽肿形成过程中起重要作用。为了分析Kupffer细胞的作用，我们比较了痤疮p.a nes处理和曼氏血吸虫可溶性蠕虫抗原制备（SWAP）处理时Kupffer细胞产生的细胞因子。未处理的Kupffer细胞通过lps产生IL-6、IL-10、IL-12、IL-18、TNF-a。痤疮诱导的Kupffer细胞通过LPS产生IL-12、IL-18、TNF-a、IL-6和IL-10。另一方面，swap刺激的Kupffer细胞通过LPS产生IL-6、IL-10、IL-12、IL-18和TNF-a。有趣的是，它们通过SWAP产生IL-4、IL-13、IL-6和IL-10。这是来自感染小鼠的Kupffer细胞在SWAP反应中产生IL-4的非常独特的事件。急性移植物抗宿主病（aGVHD）是骨髓移植的致命副作用，已被证明伴随着血清白细胞介素(IL)-18水平的升高。在这里，我们研究了IL-18在小鼠GVHD中积累的机制。用H-2异种供体脾细胞进行致命照射的受者承认aGVHD，血清IL-18水平显著升高。而受体移植的gld/gld脾细胞缺乏功能性FasL (FasL)，仅含有正常范围的IL-18，表明FasL药物在aGVHD中释放IL-18。转染caspase-1缺失细胞的野生型宿主IL-18水平明显升高，与转染野生型宿主相似，而转染caspase-1依赖细胞的野生型受体血清IL-18水平仅轻微升高，说明IL-18的升高是以caspase-1依赖的方式来源于宿主细胞。这些结果提示小鼠GVHD中fasl介导的caspase-1依赖性IL-18分泌。

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.