Inhibition of superantigen-induced apoptosis by LPS

对细菌超抗原引发的事件的研究为深入了解微生物和免疫系统之间的持续斗争提供了丰富的见解。本研究探讨了葡萄球菌肠毒素B(SEB)诱导单核细胞凋亡的机制，以及CD80~+单核细胞抗凋亡作用的一些证据。预先给予有效的NF-κB抑制剂吡咯烷二硫代氨基甲酸酯(PDTC)后，单核细胞产生的γ-和干扰素-CD802的百分率显著降低。单核细胞表达组成性的NF-κB结合活性，SEB和干扰素-γ可进一步激活NF-κB，但可被PDTC抑制。加入SEB可促进单核细胞的凋亡。SEB刺激后，sCD95配体(SCD95L)水平升高，而干扰素-γ刺激后sCD95L水平无明显变化。结果表明，SEB可诱导caspase-3和-8的激活，用广谱caspase抑制剂z-VAD-fmk处理可阻止24 h后CD80~+单核细胞的凋亡，CD80~+单核细胞对凋亡敏感，经z-VAD-fmk处理后CD80~+单核细胞存活，CD80~+单核细胞百分率降低。在干扰素-γ组中，PDTC取消了抗细胞凋亡的功能。因此，我们的结果表明，SEB的刺激既包括通过干扰素-κB激活的NF-γ的抗凋亡作用，也包括通过SEB释放的sCD95L的促凋亡作用，并且由NF-κB驱动的CD80允许单核细胞参与不同的生存计划和大量的T细胞激活。

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.