Enhancement of tumoricidal activity of microglial cell via CD40-CD40 ligand interaction

通过 CD40-CD40 配体相互作用增强小胶质细胞的杀肿瘤活性

• 批准号: 13470288
• 负责人: MORI Hiroshi
• 金额: $ 1.15万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470288/
• 关键词: microglia; glioma; CD40; IL-12; TNF-α; NO; γ-INF; IL-2; cell therapy

Purpuse) It has been reported that CD40-CD40 ligand (CD40L) interaction plays key role for cell mediated immunity on microglial cell as macropharge and dendritic cell. So we examined whether antitumor activity of microglial cell could be enhanced via CD40 induced microglial cell cocultured with CD40L transfected 203 glioma cell lines.Result) Microglial clone derived form neoborn mouse induced CD40 by combined stimulation of LPS and Interferon (IFN)-g. The following stimulation of soluble CD 40 ligand enhanced TNF-a and NO production of microglia. The supernatants from stimulated microglia via CD 40 ligation mediated killing effect against CD40 transfected 203 glioma cell line as compared to that of the stimulation by LPS, IFN-g, or LPS and IFN-g. Individually applied during CD40 ligation, anti CD40 ligand, antagonists TNF-a, or L-MNNA, or as pairs (anti TNF-a and L-MNNA) inhibited killing activity of the supernatants from stimulated microglia. This indicate that a mixture of the TNF-a and NO, or TNF-a, NO, and other factor(s) mediated significant apoptosis in tumor cell. These findings demonstrate that microglial cells induce apoptosis in tumor cells by at least two of these cytotoxic factors via CD40 engagement.

目的）据报道，CD40-CD40配体（CD40L）相互作用对于巨噬细胞和树突状细胞等小胶质细胞介导的细胞免疫发挥关键作用。因此，我们检查了是否可以通过将CD40诱导的小胶质细胞与CD40L转染的203胶质瘤细胞系共培养来增强小胶质细胞的抗肿瘤活性。结果）来自新生小鼠的小胶质细胞克隆通过LPS和干扰素(IFN)-g的联合刺激诱导CD40。可溶性 CD 40 配体的后续刺激增强了小胶质细胞的 TNF-a 和 NO 产生。与LPS、IFN-g或LPS和IFN-g刺激相比，来自通过CD 40连接刺激的小胶质细胞的上清液对CD40转染的203神经胶质瘤细胞系介导的杀伤作用。在 CD40 连接过程中单独应用抗 CD40 配体、拮抗剂 TNF-α 或 L-MNNA，或成对应用（抗 TNF-α 和 L-MNNA），可抑制刺激的小胶质细胞上清液的杀伤活性。这表明TNF-α和NO的混合物，或者TNF-α、NO和其他因子的混合物介导了肿瘤细胞中显着的细胞凋亡。这些发现表明，小胶质细胞通过 CD40 参与，通过至少两种细胞毒性因子诱导肿瘤细胞凋亡。