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前列腺素 E2 对 CD4+T 细胞免疫应答向 Th2 细胞分化的调节作用。

The regulation of CD4+ T cell immune responses toward Th2 cell development by prostaglandin E2.

机构信息

Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Int Immunopharmacol. 2011 Oct;11(10):1599-605. doi: 10.1016/j.intimp.2011.05.021. Epub 2011 May 31.

Abstract

As an important immune mediator, PGE2 plays an important role in the immune tolerance, autoimmune diseases, immune regulation and tumor immunotolerance. PGE2 is considered to be a promising candidate for the control of the immune diseases. To further understand the immuno-modulating effects of PGE2 on CD4+ T cells, in vitro investigation was conducted in the present study. The results showed that PGE2 inhibited the proliferation of T cells in vitro in a dose-dependent manner. Gene expression profiling showed that 1716 genes were down regulated and 73 genes were up regulated with a change of 1.5 fold. Several signal transduction pathways were involved, such as TNF-α and NF-kB signaling pathway, T cell receptor signaling pathway, IL-2 signaling pathway, and MAPK pathway. The results showed that PGE2 inhibited IFN-γ, TNF-α and IL-4 production by CD4+ T cells 24h after cell culture. A comparison between IFN-γ and IL-4 production showed that PGE2 enhanced the relative ratio of IL-4 to IFN-γ in CD4+ T cells culture, and regulated CD4+ T cells toward Th2 cell development. The results of the present study indicated that PGE2 has the potential to treat Th1-mediated inflammatory diseases by regulating CD4+ T cells toward Th2 cell immune response.

摘要

作为一种重要的免疫介质,PGE2 在免疫耐受、自身免疫性疾病、免疫调节和肿瘤免疫耐受中发挥重要作用。PGE2 被认为是控制免疫性疾病的有前途的候选药物。为了进一步了解 PGE2 对 CD4+T 细胞的免疫调节作用,本研究进行了体外研究。结果表明,PGE2 以剂量依赖的方式抑制 T 细胞的体外增殖。基因表达谱分析显示,有 1716 个基因下调,73 个基因上调,变化倍数为 1.5 倍。涉及多个信号转导通路,如 TNF-α和 NF-kB 信号通路、T 细胞受体信号通路、IL-2 信号通路和 MAPK 通路。结果表明,PGE2 抑制 CD4+T 细胞培养 24 小时后 IFN-γ、TNF-α和 IL-4 的产生。IFN-γ和 IL-4 产生的比较表明,PGE2 增强了 CD4+T 细胞培养中 IL-4 相对于 IFN-γ的相对比值,并调节 CD4+T 细胞向 Th2 细胞发育。本研究结果表明,PGE2 通过调节 CD4+T 细胞向 Th2 免疫反应,有可能治疗 Th1 介导的炎症性疾病。

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