Sun L, Ganea D
Department of Biological Sciences, Rutgers University, Newark, NJ 07102.
J Neuroimmunol. 1993 Oct;48(1):59-69. doi: 10.1016/0165-5728(93)90059-8.
The neuropeptide vasoactive intestinal peptide (VIP) has been reported previously to inhibit cell proliferation and interleukin (IL)-2 production in mitogen-stimulated T lymphocytes. In physiological conditions, T lymphocytes are specifically activated by antigen-binding through the T cell receptor (TCR). Here we report on the effect of VIP and related peptides on IL-2 and IL-4 production of murine T lymphocytes stimulated through the TCR. VIP inhibited IL-2 and IL-4 production (both at the level of protein concentration and biological activity) by unfractionated spleen cells or purified CD4+ T cells stimulated with either anti-CD3 monoclonal antibodies (mAbs) or with anti-CD3 mAbs plus phorbol esters. The inhibition was dose-dependent, and specific, since structurally related peptides such as secretin and glucagon had little or no inhibitory activity. VIP inhibited IL-2 and IL-4 production through different molecular mechanisms. IL-2 production was regulated at a transcriptional level through the downregulation of IL-2 mRNA, whereas the production of IL-4 was modulated at a posttranscriptional level.
先前已有报道称，神经肽血管活性肠肽（VIP）可抑制有丝分裂原刺激的T淋巴细胞中的细胞增殖和白细胞介素（IL）-2生成。在生理条件下，T淋巴细胞通过T细胞受体（TCR）与抗原结合而被特异性激活。在此，我们报告了VIP及相关肽对通过TCR刺激的小鼠T淋巴细胞产生IL-2和IL-4的影响。VIP可抑制未分级的脾细胞或纯化的CD4+ T细胞产生IL-2和IL-4（包括蛋白质浓度和生物活性水平），这些细胞用抗CD3单克隆抗体（mAb）或抗CD3 mAb加佛波酯刺激。这种抑制是剂量依赖性的且具有特异性，因为诸如促胰液素和胰高血糖素等结构相关的肽几乎没有抑制活性。VIP通过不同的分子机制抑制IL-2和IL-4的产生。IL-2的产生通过IL-2 mRNA的下调在转录水平受到调节，而IL-4的产生则在转录后水平受到调节。
