Cytocidal effect of interleukin 1 (IL-1) on HeLa cells is mediated by both soluble and transmembrane tumor necrosis factor (TNF)
Cytocidal effect of interleukin 1 (IL-1) on HeLa cells is mediated by both soluble and transmembrane tumor necrosis factor (TNF)
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DOI：
10.1016/j.cyto.2008.02.009
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发表时间：
2008-05-01
期刊：
影响因子：
3.8
通讯作者：
Bigda, Jacek J.
中科院分区：
文献类型：
--
作者：
Doszczak, Malgorzata;Pierzchalski, Arkadiusz;Bigda, Jacek J.
白细胞介素1 （IL-1）是一种多效细胞因子，能够诱导细胞杀伤作用。本研究的目的是分析il -1在环己亚胺（CHX）存在下诱导HeLa细胞的杀细胞作用机制。我们发现il -1诱导的细胞死亡模式与肿瘤坏死因子（TNF）在这些细胞中的作用有显著的相似性。随后，我们确定了IL-1的细胞毒性是间接作用。从IL-1和CHX处理的细胞中收集的上清对IL-1耐药而tnf敏感的A9细胞显示出毒性活性。此外，中和TNF的抗体可阻断IL-1/CHX诱导的HeLa细胞死亡。然后用流式细胞术、荧光显微镜和酶联免疫吸附法检测HeLa细胞中TNF的含量。在TNF脱落酶（TACE）抑制剂存在的情况下，IL-1/CHX的细胞毒作用和清洁剂可溶性细胞提取物中TNF蛋白的含量增强。这些结果表明，在对白细胞介素1/CHX的反应中，跨膜TNF的数量增加。综上所述，我们证明了在CHX存在下，IL-1在HeLa细胞中的细胞毒性活性的机制取决于可溶性和跨膜TNF的功能。(C) 2008 Elsevier Ltd版权所有。
Interleukin 1 (IL-1) is a pleiotropic cytokine able to induce cytocidal effect. The aim of the presented work was to analyze the mechanism of IL-1-induced cytocidal effect in HeLa cells in the presence of cycloheximide (CHX). We found that the pattern of IL-1-induced cell death shares significant similarities with the effect of tumor necrosis factor (TNF) in these cells. Subsequently, we identified IL-1 cytotoxicity as an indirect effect. The supernatant collected from the cells treated with IL-1 and CHX showed toxic activity towards IL-1-resistant while TNF-sensitive A9 cells. Furthermore, antibodies neutralizing TNF blocked HeLa cell death induced by IL-1/CHX. TNF was then detected in HeLa cells by means of flow cytometry, fluorescence microscopy and ELISA of detergent-soluble cell extracts. In the presence of an inhibitor of TNF sheddase (TACE), the cytotoxic effect of IL-1/CHX and the amount of TNF protein in detergent-soluble cell extracts were enhanced. These results suggest that in response to interleukin 1/CHX, the amount of transmembrane TNF is increased. Taken together, we demonstrated that the mechanism of IL-1 cytotoxic activity in HeLa cells in the presence of CHX depends on the function of soluble and transmembrane TNF. (C) 2008 Elsevier Ltd. All rights reserved.