Ganea D, Sun L
Department of Biological Sciences, Rutgers University, Newark, NJ.
J Neuroimmunol. 1993 Sep;47(2):147-58. doi: 10.1016/0165-5728(93)90025-t.
The neuropeptide vasoactive intestinal peptide (VIP) has been previously reported to inhibit T cell proliferation. Here we report on the effect of VIP on IL-2 and on IFN gamma production by murine T lymphocytes stimulated with mitogens (ConA), or activated through the antigen-specific T cell receptor. VIP inhibited IL-2 production by either unfractionated spleen cells, or by purified CD4+ T cells in a dose-dependent manner. The effect was specific, since structurally related peptides such as secretin and glucagon had little or no inhibitory effect. VIP induced a rapid increase in intracellular cAMP in CD4+ T cells, suggesting that the inhibitory effect of VIP could be mediated through the induction of cAMP. Northern blots showed that VIP downregulated IL-2 mRNA, indicating the occurrence of a transcriptional regulatory event. In contrast with its effect on IL-2, VIP did not affect IFN gamma production by either mitogen-stimulated normal T lymphocytes, or by the L12R4 murine T cell line which produces IFN gamma in response to PMA stimulation.
先前已有报道称神经肽血管活性肠肽（VIP）可抑制T细胞增殖。在此我们报告了VIP对白细胞介素-2（IL-2）以及对用丝裂原（刀豆蛋白A，ConA）刺激或通过抗原特异性T细胞受体激活的小鼠T淋巴细胞产生γ干扰素（IFNγ）的影响。VIP以剂量依赖的方式抑制未分级脾细胞或纯化的CD4 + T细胞产生IL-2。这种作用具有特异性，因为结构相关的肽如促胰液素和胰高血糖素几乎没有抑制作用。VIP可使CD4 + T细胞内的细胞内环状单磷酸腺苷（cAMP）迅速增加，这表明VIP的抑制作用可能是通过诱导cAMP介导的。Northern印迹显示VIP下调IL-2信使核糖核酸（mRNA），表明发生了转录调节事件。与它对IL-2的作用相反，VIP对丝裂原刺激的正常T淋巴细胞或对经佛波酯（PMA）刺激产生IFNγ的L12R4小鼠T细胞系产生IFNγ没有影响。
