Vasoactive intestinal peptide inhibits interleukin (IL)-2 and IL-4 production through different molecular mechanisms in T cells activated via the T cell receptor/CD3 complex.
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.
Sun
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Department of Biological Sciences, Rutgers University, Newark, NJ 07102.
Ganea
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D007376:Interleukin-2; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015847:Interleukin-4; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP