Differential expression of the Fas-Fas ligand system on cytokine-induced apoptotic cell death in mouse osteoblastic cells
Differential expression of the Fas-Fas ligand system on cytokine-induced apoptotic cell death in mouse osteoblastic cells
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DOI：
10.1016/s0003-9969(02)00035-3
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发表时间：
2002-07-01
影响因子：
3
通讯作者：
Togari, A
中科院分区：
文献类型：
--
作者：
Ozeki, N;Mogi, M;Togari, A
在小鼠成骨细胞系MC 3 T3-E1中研究了凋亡信号传导，特别是在Fas-Fas配体（FasL）系统中。细胞因子肿瘤坏死因子-α、白细胞介素-1 β和干扰素-γ的组合激活了Fas-FasL依赖性细胞死亡系统。细胞因子可引起Fas mRNA和Fas蛋白表达明显增强，并导致细胞凋亡。Western blot结果显示，FasL蛋白在MC 3 T3-E1细胞中持续表达，细胞因子对FasL的诱导无影响。外源性FasL导致细胞活力下降和细胞凋亡细胞死亡的细胞因子预处理的细胞中的大量增加，表明Fas-FasL系统有可能导致成骨细胞凋亡。用抗Fas IgG（拮抗性抗体）处理以剂量依赖方式抑制细胞因子诱导的DNA片段化，表明苦参碱诱导的Fas可能导致MC 3 T3-E1细胞凋亡。总之，这些研究结果表明，苦参碱诱导的细胞凋亡是由小鼠成骨细胞中的自分泌或旁分泌Fas-FasL系统介导的，并表明苦参碱诱导的细胞凋亡可能在与炎症性骨疾病如牙周病相关的局部骨破坏中起重要作用。(C)2002爱思唯尔科技有限公司版权所有。
Apoptotic signalling, particularly in the Fas-Fas ligand (FasL) system, was studied in a mouse osteoblastic cell line, MC3T3-E1. A combination of the cytokines tumour necrosis factor-alpha, interleukin-1beta and interferon-gamma activated the Fas-FasL-dependent cell-death system. The cytokines caused significant enhancement of Fas mRNA and Fas protein, and led to apoptotic cell death. Western blot demonstrated that FasL protein was continuously present in MC3T3-E1 cells, although the cytokines had no effect on the induction of FasL. Exogenous FasL caused a decrease in cell viability and a large increase in apoptotic cell death in cells pre-treated with cytokines, indicating that the Fas-FasL system has the potential to cause apoptosis in osteoblastic cells. Treatment with anti-Fas IgG (antagonistic antibody) inhibited the DNA fragmentation induced by cytokines in a dose-dependent manner, suggesting that cytokine-induced Fas may cause apoptotic cell death in MC3T3-E1 cells. Taken together, these findings show that cytokine-induced apoptotic cell death was mediated by the autocrine or paracrine Fas-FasL system in mouse osteoblastic cells, and suggest that cytokine-induced apoptosis could have an important role in localised bone destruction associated with inflammatory bone diseases such as periodontal disease. (C) 2002 Elsevier Science Ltd. All rights reserved.