HDAC抑制剂丙戊酸对小鼠T淋巴细胞表达细胞因子的影响

The effects of the histone deacetylase inhibitor valproic acid on cytokine synthesis of mouse T lymphocytes

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。

This study aims to investigate the effects of histone deacetylase（HDAC） inhibitor valproic acid（VPA） on the syntheses of IL-2,IFN-γ and IL-6 of mouse T lymphocyte subpopulations,and to elucidate the mechanism of the anti-inflammatory and immunomodulatory effects of VPA.The lymphocytes were stimulated with phorbol ester（PDB） and inomycin in the presence or absence of different concentrations VPA,and the syntheses of IL-2,IFN-γ and IL-6 of different subsets of mouse T lymphocytes were analyzed by flow cytometry.The results demonstrated that after the stimulation of PDB and ionomycin,IL-6 expression was increased slightly,while IL-2＋ rate in CD4＋ and CD8＋ T cells were 35.49% and 5.50% respectively and IFN-γ＋ rate were 3.47% and 38.60% respectively.VPA obviously reduced the expression rate of IL-6＋,IFN-γ＋ and IL-6＋IFN-γ＋ in CD3＋ T cells in a dose-dependent manner（P 0.01）.Similarly,VPA dose-dependently diminished the percentage of CD4＋ and CD8＋ T cell subsets that expressing IL-2＋ and IFN-γ＋（P 0.01）.There were similar inhibitory effects on the IL-2＋IFN-γ＋ double positive CD4＋ and CD8＋ T cells（P 0.01）.Moreover,the inhibitory effects of VPA on the expression of IFN-γ in CD8＋ T cells were stronger than that in CD4＋ T cells.These data indicate that HDAC inhibitor VPA may mediate anti-inflammatory and immunomodulatory effects through inhibiting the expression of IL-2 and IFN-γ.