全反式维甲酸对Th2极化的调节作用

All-Trans Retionic Acid Regulates Polarization of Th2

为了研究全反式维甲酸(all-trans retinoic acid,ATRA)对Th细胞分化的影响和可能的机制,无菌分离BALB/c小鼠脾细胞后,用2.5μg/ml的ConA刺激脾细胞,在不同时间加入不同剂量的ATRA,72 h后收集细胞,用3H-TdR掺入法测淋巴细胞增殖活性,用RT-PCR方法检测在Th细胞分化中起作用的细胞因子的mRNA表达水平。结果ATRA呈剂量依赖抑制ConA诱导的淋巴细胞的活化,10^(-5)mol/L的ATRA对ConA诱导的淋巴细胞活化的抑制作用最强;此抑制作用与作用时间呈相关性,ConA活化淋巴细胞24 h后加入ATRA对淋巴细胞活化的抑制作用最显著,并且淋巴细胞的活化程度越低,ATRA对其的抑制作用越强。ATRA可增强经ConA活化的淋巴细胞Th2型细胞因子(IL-4、IL-6)mRNA的表达水平,而Th1型细胞因子(IFN-γ、TNF-α)mRNA的表达水平显著性降低(P<0.05)。上述结果表明ATRA总体上可抑制ConA刺激的淋巴细胞增殖活性,但却可增强,Th2细胞的分化。这一研究为Th细胞免疫偏离的基础与临床研究提供了依据。

To investigate the effect of ATRA on the differentiation of Th cells and possible mechanisms involved in, spleen cells derived from BALB/c mice were isolated and stimulated by 2.5μg/ml of ConA. ATRA with different concentrations were then added at different time points. The proliferation of spleen cells was measured by 3H-TdR incorporation assay, and the level of mRNA transcripped for the cytokines involved in differentiation of Th cells was detected by RT-PCR. The results showed that ATRA inhibited the ConA-induced proliferation of lymphocytes in a dose-dependent manner with the ATRA of 10-5mol/L the strongest. The inhibitory effect of ATRA was associated with the time when A-TRA was added. When ATRA was added 24 hours after ConA activation, the inhibitory effect of ATRA was the most significant . Furthermore, the more the cells were activated, the stronger the inhibitory effect was. ATRA enhanced mRNA for genes involved in Th2 development (IL-4, IL-6 ) and decreased mRNA for genes involved in Th 1 development (IFN-γ, TNF-α )significantly ( P < 0.05 ) . Thus, ATRA inhibits the ConA-induced the proliferation of lymphocytes and enhances the development of Th2 providing some evidences for the application of ATRA to therapy of some diseases of dysfunction of T cells in clinic.