Vasoactive intestinal peptide inhibits cytokine production in T lymphocytes through cAMP-dependent and cAMP-independent mechanisms

Hong Ying Wang, Xiaoming Jiang, Illana Gozes, Mati Fridkin, Douglas E. Brenneman, Doina Ganea

Research output: Contribution to journalArticlepeer-review

Abstract

Previous reports indicate that VIP and the structurally related peptide PACAP, inhibit IL-2 and IL-10 production in antigen-stimulated T lymphocytes. Intracellular cAMP elevation appears to be the primary transduction pathway involved. However, in the lower concentration range, an additional, cAMP-independent transduction pathway appears to mediate the VIP inhibition of cytokine production. Here, we address this question by using VIP agonists and antagonists which act through cAMP-dependent and -independent pathways. The antagonists based on the neurotensin-VIP hybrid molecule did not affect the inhibitory effect of VIP/PACAP on IL-2 and IL-10 production, confirming that astrocytes and T lymphocytes express different receptors. A lipophilic antagonist with increased membrane permeability, partially reversed the inhibitory effect of VIP/PACAP, forskolin, prostaglandin E2, and 8-bromo-cAMP without significantly affecting cAMP levels, suggesting that it acts downstream of cAMP. Two VIP inhibit agonists IL-2 and IL-10 production. One of the agonists increases cAMP, whereas the second one does not induce cAMP/cGMP. Our results indicate that VIP inhibits cytokine production in stimulated CD4+ T cells through two separate mechanisms, which involve both cAMP-dependent and cAMP-independent transduction pathways. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)55-67
Number of pages13
JournalRegulatory Peptides
Volume84
Issue number1-3
DOIs
StatePublished - 22 Oct 1999

Keywords

  • -antagonists
  • IL-10
  • IL-2
  • PACAP
  • Transduction pathways.
  • VIP-agonists

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