Differential effect of IL-18 on endothelial cell apoptosis mediated by TNF-α and Fas (CD95)
Differential effect of IL-18 on endothelial cell apoptosis mediated by TNF-α and Fas (CD95)
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DOI：
10.1016/s1043-4666(03)00150-9
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发表时间：
2003-06-07
期刊：
影响因子：
3.8
通讯作者：
Cardier, JE
中科院分区：
文献类型：
--
作者：
Mariño, E;Cardier, JE
白介素18(IL-18)是新近发现的一种具有促炎活性的细胞因子。大量研究表明，促炎细胞因子可调节肿瘤坏死因子家族成员如肿瘤坏死因子-α和Fas等介导的内皮细胞凋亡。在本研究中，我们假设IL-18可能调节肝内皮细胞对肿瘤坏死因子和Fas诱导的细胞凋亡的敏感性。IL-18可增加LEC对肿瘤坏死因子而不是Fas介导的细胞凋亡的敏感性。由于肿瘤坏死因子诱导的细胞凋亡是由I型肿瘤坏死因子受体(TNFRI)介导的，我们研究了该受体在IL-18处理的LEC中的上调作用。IL-18诱导LEC表面TNFRI表达上调。Caspase广谱抑制剂z-VAD-fmk可部分阻断IL-18和TNF诱导的LEC凋亡，提示caspase途径参与了这些细胞因子诱导的LEC的凋亡。结果表明，IL-18对肿瘤坏死因子和Fas等死亡诱导因子介导的细胞凋亡有不同的调节作用。据我们所知，IL-18可能调节肿瘤坏死因子介导的内皮细胞凋亡的报道尚属首次。这些结果可能对那些与高水平IL-18和肿瘤坏死因子相关的临床肝病具有临床意义。(C)2003爱思唯尔有限公司。保留所有权利。
Interleukin-18 (IL-18) is a newly identified cytokine with proinflammatory activity. Numerous studies have shown that proinflammatory cytokines may regulate endothelial cells (EC) apoptosis mediated by members of the tumor necrosis factor (TNF) family, such as TNF-alpha and Fas. In this study we hypothesized that IL-18 may regulate the susceptibility of liver endothelial cells (LEC) to apoptosis induced by TNF and Fas. IL-18 increased the susceptibility of LEC to undergo apoptosis mediated by TNF but not by Fas. Since TNF-induced apoptosis is mediated by the type I TNF receptor (TNFRI), we investigated up-regulation of this receptor in IL-18-treated LEC. IL-18 induced up-regulation of the TNFRI on the surface of LEC. Partial blocking of LEC apoptosis induced by IL-18 and TNF was observed when the cells were pretreated with the broad-spectrum inhibitor of caspases z-VAD-fmk, suggesting involvement of the caspase pathway in apoptosis induced by these cytokines in these cells. Our results show that IL-18 differentially regulates apoptosis mediated by the death-inducing factors, TNF and Fas. To our knowledge, this is the first report that IL-18 may regulate endothelial cell apoptosis mediated by TNF. These results may have clinical implications in those clinical hepatic conditions associated with high levels of IL-18 and TNF. (C) 2003 Elsevier Ltd. All rights reserved.