Vasoactive intestinal peptide (VIP) inhibits TGF-beta 1 production in murine macrophages

Vasoactive intestinal peptide (VIP) and the structurally related neuropepti de pituitary adenylate cyclase-activating polypeptide (PACAP), produced and /or released in the lymphoid microenvironment act primarily as macrophage- and T cell-deactivating agents. In the present study we investigate the eff ect of VIP and PACAP on the production of TGF-beta 1 in the macrophage cell line Raw 264.7 and in peritoneal macrophages. The two neuropeptides do not affect the baseline TGF-beta 1 production by unstimulated macrophages, but reduce dramatically TGF-beta 1 production by LPS-stimulated macrophages. T he effects are mediated through the specific receptors VPAC1. VPAC2. and PA C1. The effect of VIP is mediated primarily through the cAMP pathway, where as PACAP activates both the cAMP and the protein kinase C pathway. VIP redu ces the TGF-beta 1 steady-state mRNA levels in both peritoneal macrophages and Raw 264.7 cells treated with LPS. A similar effect is observed upon the in vivo administration of VIP. This report adds VIP and PACAP to the only other neuropeptide, substance P, known to regulate TGF-beta 1 production in immune cells. (C) 1000 Elsevier Science B.V. All rights reserved.