Vasoactive intestinal peptide downregulates the expression of IL-2 but not of IFN gamma from stimulated murine T lymphocytes.
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.
Ganea
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Department of Biological Sciences, Rutgers University, Newark, NJ.
Sun
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D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D017252:CD3 Complex; D007376:Interleukin-2; D011994:Recombinant Proteins; D003208:Concanavalin A; D015847:Interleukin-4; D014660:Vasoactive Intestinal Peptide; D007371:Interferon-gamma; D000242:Cyclic AMP