TY - JOUR
T1 - Vasoactive intestinal peptide inhibits cytokine production in T lymphocytes through cAMP-dependent and cAMP-independent mechanisms
AU - Wang, Hong Ying
AU - Jiang, Xiaoming
AU - Gozes, Illana
AU - Fridkin, Mati
AU - Brenneman, Douglas E.
AU - Ganea, Doina
N1 - Funding Information:
This work was supported in part by the Charles & Johanna Busch Biomedical Award (DG), and by the PHS grants MH49079-01A3, AI41786-01R21, and AI41786-02(DG). We thank Dr. Patrick Robberecht (Universite Libre de Bruxelles, Belgium) for his generous gift of [R 16 ]-chicken secretin, and Drs. Ann Welton and D.R. Bolin (Hoffmann-La Roche Inc., Nutley, NJ) for their gift of RO 25-1553 and RO 25-1392.
PY - 1999/10/22
Y1 - 1999/10/22
N2 - 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.
AB - 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.
KW - -antagonists
KW - IL-10
KW - IL-2
KW - PACAP
KW - Transduction pathways.
KW - VIP-agonists
UR - http://www.scopus.com/inward/record.url?scp=0032830273&partnerID=8YFLogxK
U2 - 10.1016/S0167-0115(99)00068-3
DO - 10.1016/S0167-0115(99)00068-3
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AN - SCOPUS:0032830273
SN - 0167-0115
VL - 84
SP - 55
EP - 67
JO - Regulatory Peptides
JF - Regulatory Peptides
IS - 1-3
ER -