Selective apoptosis during treatment with superantigen and lipopolysaccharide

超抗原和脂多糖治疗期间的选择性细胞凋亡

• 批准号: 14571726
• 负责人: RIKIISHI Hidemi
• 金额: $ 1.79万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571726/
• 关键词: Superantigen; Lipopolysaccharide; Apoptosis; CD80; Gingival tissue; Fas; FasL; NF-κB; Cytokine; LPS; カスパーゼ

Studies of the events triggered by bacterial superantigens and lipopolysaccharide (LPS) provide rich insight into the constant battle between microbes and the oral immune system. In this study, we demonstrated a mechanism of apoptosis induced by staphylococcal enterotoxin B (SEB) in cultured monocytes and gingival fibroblasts, and some evidence for the anti-apoptotic function in CD80^+ monocytes. Apoptosis of monocytes was accelerated and enhanced by the addition of SEB. Increases in soluble CD95 ligand (sCD95L) levels were observed with stimulation with SEB, but not gamma interferon (IFN-γ). Our results clearly demonstrated that SEB treatment induces the activation of caspase-3 and -8, and pretreatment with zVAD-FMK, a broad inhibitor of caspases, prevented the induction of apoptosis at 24 h. Monocytes expressed constitutive NF-κB binding activity, and SEB further activated NF-κB, which was inhibited by pretreatment with pyrrolidine dithiocarbamate even at dose of 5 μM. PDTC markedly stimulated apoptosis induced by SEB and induced apoptosis in those treated with IFN-γ. Marked inhibition of the appearance of CD80^+ monocytes was achieved by treating cells with zVAD-FMK and DEVD-FMK, which was paralleled by reduced apoptosis of monocytes. LPS treatment resulted in significant reduction of the percentage of SEB-or IFN-γ induced apoptosis through induction of anti-apoptotic protein XIAP. Thus, our results indicated that SEB stimulation includes both anti-apoptotic actions through NF-κB activation and pro-apoptotic actions through sCD95L released by SEB, and that CD80 driven by NF-κB allows gingival tissues to participate in distinct survival programs.

对细菌超抗原和脂多糖（LPS）引发的事件的研究为微生物和口腔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）诱导培养的单核细胞和牙龈成纤维细胞凋亡的机制，以及CD 80 ^+单核细胞抗凋亡功能的一些证据。SEB的加入促进单核细胞凋亡。用SEB刺激观察到可溶性CD 95配体（sCD 95 L）水平增加，但未观察到γ干扰素（IFN-γ）。我们的结果清楚地表明，SEB处理诱导caspase-3和-8的活化，并且用caspase的广泛抑制剂zVAD-FMK预处理，在24 h阻止了凋亡的诱导。单核细胞表达组成性NF-κB结合活性，SE B进一步激活NF-κB，即使在5 μM的剂量下，吡咯烷二硫代氨基甲酸酯预处理也能抑制NF-κB的活性。PDTC可明显促进SEB诱导的细胞凋亡，并诱导IFN-γ诱导的细胞凋亡。用zVAD-FMK和DEVD-FMK处理细胞，可以显著抑制CD 80 ^+单核细胞的出现，并减少单核细胞的凋亡。LPS处理可通过诱导抗凋亡蛋白XIAP的表达，显著降低SEB-或IFN-γ诱导的细胞凋亡百分率。因此，我们的研究结果表明，SE B刺激包括通过NF-κB激活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允许牙龈组织参与不同的存活程序。

项目成果

Maiko Suzuki: "Interleukin-1β converting enzyme subfamily inhibitors prevent induction of CD86 molecules by butyrate through a CREB-dependent mechanism in HL6O cells."Immunology. 108(3). 375-383 (2003)

Maiko Suzuki：“IL6O 细胞中白细胞介素 1β 转换酶亚家族抑制剂通过 CREB ​​依赖性机制阻止丁酸诱导 CD86 分子。”免疫学 108(3) 375-383 (2003)。

M.Suzuki: "Interleukin-1β converting enzyme subfamily inhibitors prevent induction of CD86 molecules by butyrate through a CREB-dependent mechanism in HL60 cells"Immunology. 108(3). 375-383 (2003)

M.Suzuki：“IL60 细胞中白细胞介素 1β 转换酶亚家族抑制剂通过 CREB ​​依赖性机制阻止丁酸诱导 CD86 分子”免疫学 108(3) (2003)。

H.Rikiishi: "Role of caspase in regulation of B7 costimulatory molecules of monocytic cells"Recent Research Developments in Immunology. 5. 115-129 (2003)

H.Rikiishi：“半胱天冬酶在单核细胞 B7 共刺激分子调节中的作用”免疫学的最新研究进展。

Hidemi Rikiishi: "Role of caspase in regulation of B7 costimulatory molecules of monocytic cells"Recent Research Developments in Immunology. 5. 115-129 (2003)

Hidemi Rikiishi：“半胱天冬酶在单核细胞 B7 共刺激分子调节中的作用”免疫学的最新研究进展。

Maiko Suzuki: "Interleukin-1β converting enzyme subfamily inhibitors prevent induction of CD86 molecules by butyrate through a CREB-dependent mechanism in HL6O cells"Immunology. 108(3). 375-383 (2003)

Maiko Suzuki：“IL6O 细胞中白细胞介素 1β 转换酶亚家族抑制剂通过 CREB ​​依赖性机制阻止丁酸诱导 CD86 分子”免疫学 108(3)。