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目的分析组蛋白去乙酰化酶(HDAC)抑制剂丙戊酸(Valproic acid,VPA)对小鼠T细胞亚群IL-2、IFN-γ和IL-6表达的影响,探讨其抗炎免疫调节作用的机制。方法经VPA处理小鼠淋巴细胞,并在佛波醇酯(PDB)和离子霉素刺激后,以流式细胞术分析CD3+、CD4+和CD8+T细胞表达IL-2、IFN-γ和IL-6的情况。结果淋巴细胞受刺激后,IL-6的表达水平仅稍有提高,而IL-2在CD4+和CD8+T细胞表达率分别为35.49%和5.50%,IFN-γ表达率分别为3.47%和38.60%。经VPA处理后,CD3+T细胞IL-6+、IFN-γ+和IL-6+IFN-γ+的表达均受剂量依赖性抑制(P<0.01)。同样,VPA能够剂量依赖性地降低小鼠CD4+和CD8+T细胞亚群内表达IL-2+、IFN-γ+的细胞比例(P<0.01),对于IL-2+IFN-γ+双阳性细胞的比例也具有明显抑制作用(P<0.01);此外,VPA对CD8+T细胞表达IFN-γ的抑制程度高于CD4+T细胞。结论 HDAC抑制剂VPA通过抑制IL-2和IFN-γ而发挥其抗炎和免疫调节效应。
Objective To investigate the effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on the expression of IL-2, IFN-γ and IL-6 in T lymphocyte subsets of mice and to investigate its anti-inflammatory immune regulation Mechanism of action. Methods The lymphocytes of mice were treated with VPA, and the expressions of IL-2, IFN-γ and IL-10 in CD3 +, CD4 + and CD8 + T cells were analyzed by flow cytometry after stimulation with phorbol ester (PDB) and ionomycin 6 situation. Results The expression level of IL-6 was only slightly increased after lymphocyte stimulation, while the expression rates of IL-2 in CD4 + and CD8 + T cells were 35.49% and 5.50% respectively, and the expression rates of IFN-γ were 3.47% and 38.60 %. After VPA treatment, the expression of IL-6 +, IFN-γ + and IL-6 + IFN-γ + of CD3 + T cells were inhibited in a dose-dependent manner (P <0.01). Similarly, VPA decreased the proportion of cells expressing IL-2 + and IFN-γ + in CD4 + and CD8 + T lymphocytes in a dose-dependent manner (P <0.01), while double positive for IL-2 + IFN- (P <0.01). In addition, the inhibitory effect of VPA on CD8 + T cells expressing IFN-γ was higher than that of CD4 + T cells. Conclusion HDAC inhibitor VPA exerts its anti-inflammatory and immunomodulatory effects by inhibiting IL-2 and IFN-γ.