Vasoactive intestinal peptide stimulates p59fyn kinase activity in murine thymocytes

The neuropeptide VIP has immunomodulatory properties, including the inhibition of cytokine production (IL-2, IL-4, and IL-10) in T lymphocytes stimulated through their TCR. The transduction pathways involved in the inhibitory effect of VIP on IL-2 expression are not known. Here we investigate the effect of VIP on the T-cell-specific protein tyrosine kinases p56lck and p59fyn in resting and stimulated thymocytes. VIP does not affect lck or fyn activity in stimulated thymocytes and does not alter the general pattern of cellular tyrosine phosphorylation. However, VIP stimulates p59fyn, but not p56lck, kinase activity in resting thymocytes. The effect is dose dependent, exhibits a specific time course, and is reproduced by other cAMP-inducing agents such as forskolin, prostaglandin E2, and 8-bromo-cAMP, suggesting that cAMP may function as the intracellular mediator.