Interferon-γ-induced apoptosis and activation of THP-1 macrophages
Interferon-γ-induced apoptosis and activation of THP-1 macrophages
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DOI：
10.1016/s0024-3205(02)02042-8
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发表时间：
2002-10-11
期刊：
影响因子：
6.1
通讯作者：
Makita, Z
中科院分区：
文献类型：
--
作者：
Inagaki, Y;Yamagishi, S;Makita, Z
凋亡巨噬细胞在人类动脉粥样硬化病变中经常被观察到，并且被认为参与动脉粥样硬化斑块不稳定。然而，动脉粥样硬化中促进巨噬细胞程序性死亡的分子机制仍有待阐明。在这项研究中，我们研究了干扰素- γ (ifn - γ)对THP-1巨噬细胞凋亡细胞死亡的影响，干扰素- γ是一种由活化的T辅助细胞1 （Th1）分泌的细胞因子。我们进一步研究了这些凋亡的巨噬细胞是否可以在体外同时被激活并随后过度产生单核细胞化学引诱蛋白-1 （MCP-1）。当THP-1巨噬细胞与不同浓度的ifn - γ培养时，DNA合成明显降低。发现ifn - γ显著诱导THP-1巨噬细胞凋亡。RNase保护实验显示，lfn - γ上调THP-1细胞中两种促凋亡分子肿瘤坏死因子α受体I （TNFR1）和caspase-8的mRNA水平。此外，发现tnf - α抗体完全中和ifn - γ诱导的巨噬细胞DNA合成抑制和凋亡细胞死亡。发现ifn - γ激活这些巨噬细胞以刺激MCP-1的产生。结果表明，ifn - γ不仅对巨噬细胞具有凋亡作用，还能激活巨噬细胞并导致MCP-1过度生成，从而参与动脉粥样硬化的发生和进展。(C) 2002爱思唯尔科学有限公司版权所有。
Apoptotic macrophages are frequently observed in human atherosclerotic lesions, and are considered to be involved in plaque instability in atherosclerosis. However, the molecular mechanism that promotes programmed cell death of macrophages in atherosclerosis remains to be elucidated. In this study, we investigated the effects of interferon-gamma (IFN-gamma), a cytokine secreted by activated T helper 1 (Th1) lymphocytes, on apoptotic cell death of THP-1 macrophages. Further we studied whether these apoptotic macrophages could be simultaneously activated in vitro and subsequently overgenerate monocyte chemoattractant protein-1 (MCP-1). When THP-1 macrophages were cultured with various concentrations of IFN-gamma, DNA synthesis was significantly decreased. IFN-gamma was found significantly to induce apoptotic cell death in THP-1 macrophages. RNase protection assay revealed that lFN-gamma up-regulated the mRNA levels of two pro-apoptotic molecules, tumor necrosis factor-alpha receptor I (TNFR1) and caspase-8, in THP-1 cells. Furthermore, TNF-alpha antibodies were found completely to neutralize the IFN-gamma-induced inhibition in DNA synthesis as well as apoptotic cell death in macrophages. IFN-gamma was found to activate these macrophages to stimulate MCP-1 production. The results suggest that IFN-gamma not only exerted apoptotic effects on macrophages, but also activated them and subsequently overgenerated MCP-1, and was thus involved in the development and progression of atherosclerosis. (C) 2002 Elsevier Science Inc. All rights reserved.