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Inhibition of superantigen-induced apoptosis by LPS

LPS 抑制超抗原诱导的细胞凋亡

基本信息

批准号：
12671759
负责人：
RIKIISHI Hidemi
金额：
$ 2.18万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671759/
关键词：
Superantigen LPS Apoptosis CD80 Monocyte Fas Fas L カスパーゼインターフェロンγ

项目摘要

Studies of the events triggered by bacterial superantigens provide rich insight into the constant battle between microbes and the immune system. In this study, we demonstrated a mechanism of apoptosis induced by staphylococcal enterotoxin B (SEB) in monocytes and some evidence for the anti-apoptotic function in CD80^+ monocytes. Pretreatment with pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-κB, resulted in significant reduction of the percentages of SEB-and IFN-γ (produced by SEB)-induced CD80^+ monocytes. Monocytes expressed constitutive NF-κB binding activity, and SEB and IFN-γ further activated NF-κB, which was inhibited by pretreatment with PDTC. Apoptosis of monocytes was enhanced by the addition of SEB. Increases in soluble CD95 ligand (sCD95L) levels were observed following stimulation with SEB, but not IFN-γ. Our results demonstrated that SEB treatment induced the activation of caspase-3 and -8, and pretreatment with z-VAD-fmk, a broad-spectrum inhibitor of caspases, prevented the induction of apoptosis at 24 h. CD80^- monocytes were sensitive to apoptosis, and survival of CD80^- monocytes from apoptosis by treating with z-VAD-fmk resulted in reduction of the percentages of CD80^+ monocytes. PDTC abolished anti-apoptotic function in those treated with IFN-γ. Thus, our results indicated that SEB stimulation includes both anti-apoptotic action through NF-κB activation by IFN-γ and pro-apoptotic action through sCD95L released by SEB, and that CD80 driven by NF-κB allows monocytes to participate in distinct survival programs and massive T-cell activation.

对细菌超抗原引发的事件的研究为微生物和免疫系统之间的持续战斗提供了丰富的见解。在这项研究中，我们证明了葡萄球菌肠毒素B（SE B）诱导单核细胞凋亡的机制，并证明了CD 80 ^+单核细胞的抗凋亡功能。用NF-κB的强效抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）预处理可显著降低SEB-和IFN-γ（由SE B产生）诱导的CD 80 ^+单核细胞的百分比。单核细胞表达组成型NF-κB结合活性，SE B和IFN-γ进一步激活NF-κB，PDTC预处理可抑制NF-κB结合活性。SEB的加入可促进单核细胞凋亡。用SEB刺激后观察到可溶性CD 95配体（sCD 95 L）水平增加，但IFN-γ未观察到。我们的结果表明，SEB处理诱导caspase-3和-8活化，和z-VAD-fatty acid预处理，一种广谱的caspase抑制剂，阻止诱导的凋亡在24小时。CD 80 ^-单核细胞对细胞凋亡敏感，用z-VAD-fatty acid处理后，CD 80 ^-单核细胞从细胞凋亡中存活下来，导致CD 80 ^+单核细胞的百分比降低。PDTC可阻断IFN-γ治疗组的抗凋亡功能。因此，我们的结果表明，SE B刺激包括通过IFN-γ激活NF-κB的抗凋亡作用和通过SE B释放的sCD 95 L的促凋亡作用，并且NF-κB驱动的CD 80允许单核细胞参与不同的存活程序和大量T细胞活化。