Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Int Immunopharmacol. 2011 Oct;11(10):1599-605. doi: 10.1016/j.intimp.2011.05.021. Epub 2011 May 31.
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.
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。