霉酚酸对趋化性细胞因子I-TAC的表达及其功能的影响

研究探讨霉酚酸(MPA)对趋化性细胞因子I-TAC的表达及其功能的影响。分别在IFN-γ加入之前、同时、之后加MPA于培养的ECV-304细胞中,以RT-PCR检测其I-TAC mRNA的表达水平。PBMC经不同浓度MPA(10、100、1 000ng/ml)处理12 h后,采用微迁移板技术观察MPA对I-TAC趋化作用的影响。MTT法测定不同浓度MPA(10、100、1 000ng/ml)对I-TAC促PBMC增殖效应的影响。结果显示,在不同时间加入MPA处理的各组,其I-TAC/GAPDH比值均显著地小于对照组(P<0.01),而MPA处理组之间无显著性差异(P>0.05)。MPA处理组PBMC的迁移指数和MTT试验的A值与相应对照组相比均显著下降(P<0.05)。这些结果提示,MPA对I-TAC在内皮细胞上表达及其趋化、促增殖功能具有抑制作用。MPA的这些新发现的功能可能是霉酚酸酯(MMF)抗移植排斥的重要机制之一。

Effect of mycophenolate acid on the expression and functions of IFN-inducible T cell α-chemoattractant

To investigate the effect of mycophenilic acid(MPA) on the expression and function of IFN-inducible T cell α-chemoattractant(I-TAC),MPA was added to the human umbilical vein endothelial cells(ECV-304) cultures,prior to,simultaneously and after the addition of IFN-γ,respectively,and the expression of the I-TAC mRNA was detected by RT-RCR.Meanwhile,the migration of peripheral blood mononuclear cells(PBMC) recruited by I-TAC was determined by use of the chemotaxis chamber after the cells were treated with different concentrations of MPA for 12 hrs.Similar treatment was applied to PBMC culture to observe the potential of MPA in altering the proliferation of PBMC as detected by the MTT assay. It was found that the I-TAC/GAPDH ratios in cases of MPA added at different periods were significantly smaller than that of the controls,but there showed no significant difference among the different groups with addition of MPA.The chemotactic indices of PBMC and the A values in MTT assay with absorbance at 490 nm of the MPA-treated groups were all significantly reduced in comparison with that of the control group.It is thus concluded that MPA is able to inhibit the expression of I-TAC and to impact its function in chemotaxis and the promotion of cell proliferation.The properties of PMA observed in the present study would help to reveal a new mechanism involved in the anti-rejection effect of MPA and other immunosuppressive agents in organ transplantation.