IL-18 induces apoptosis of adherent bone marrow cells in TNF-α mediated osteoclast formation in synergy with IL-12
IL-18 induces apoptosis of adherent bone marrow cells in TNF-α mediated osteoclast formation in synergy with IL-12
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DOI：
10.1016/j.imlet.2006.06.005
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Nakayama, Koji
中科院分区：
文献类型：
--
作者：
Kitaura, Hideki;Tatamiya, Mutsuhito;Nakayama, Koji
最近有报道称，肿瘤坏死因子-α具有促进破骨细胞生成的作用。我们先前报道，促炎细胞因子IL-12通过Fas和Fas配体(FasL)的相互作用在肿瘤坏死因子-α介导的小鼠骨髓破骨细胞生成中诱导细胞凋亡。本研究探讨IL-18在肿瘤坏死因子-α介导的破骨细胞生成中的作用。当小鼠骨髓细胞同时与肿瘤坏死因子-α和白介素18共同培养时，贴壁细胞数量减少。在贴壁细胞中观察到了凋亡效应，以核、细胞和DNA片段化为标志。抗FasL抗体可抑制细胞凋亡。Fas-FasL相互作用可能导致贴壁的骨髓细胞发生凋亡。此外，IL-18和IL-12在有肿瘤坏死因子-α存在的情况下协同诱导贴壁的骨髓细胞凋亡，并上调非贴壁细胞的FasL转录。结果提示，IL-12和IL-18协同上调FasL可促进贴壁细胞的凋亡。(C)2006爱思唯尔B.V.保留所有权利。
It has recently been reported that TNF-alpha has the ability to accelerate osteoclastogenesis. We previously reported that the proinflammatory cytokine IL-12 induced apoptosis in TNF-alpha-mediated osteoclastogenesis in mouse bone marrow culture through an interaction of Fas and Fas ligand (FasL). In this study, the effect of IL-18 was investigated, which is also a proinflammatory cytokine, on TNF-alpha-mediated osteoclastogenesis. When mouse bone marrow cells were cultured with both TNF-alpha and IL-18, the number of adherent cells in the culture decreased. Apoptotic effects, indicated by nuclear, cellular and DNA fragmentation, were observed in the adherent cells. The apoptosis was inhibited by an anti-FasL antibody. Apoptosis of the adherent bone marrow cells might be caused by Fas-FasL interactions. Furthermore, IL-18 and IL-12 synergistically induced apoptosis of adherent bone marrow cells in the presence of TNF-alpha, and up-regulated FasL transcription in non-adherent cells. The results suggested that FasL synergistically up-regulated by IL-12 and IL-18 increased apoptosis of the adherent cells. (c) 2006 Elsevier B.V. All rights reserved.