Vasoactive intestinal peptide (VIP) inhibits TGF-beta1 production in murine macrophages.
Vasoactive intestinal peptide (VIP) and the structurally related neuropeptide 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 effect of VIP and PACAP on the production of TGF-beta1 in the macrophage cell line Raw 264.7 and in peritoneal macrophages. The two neuropeptides do not affect the baseline TGF-beta1 production by unstimulated macrophages, but reduce dramatically TGF-beta1 production by LPS-stimulated macrophages. The effects are mediated through the specific receptors VPAC1, VPAC2, and PAC1. The effect of VIP is mediated primarily through the cAMP pathway, whereas PACAP activates both the cAMP and the protein kinase C pathway. VIP reduces the TGF-beta1 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-beta1 production in immune cells.
Sun
W
W
Department of Biological Sciences, Rutgers University, 101 Warren St. , Newark, NJ 07102, USA.
Tadmori
I
I
Yang
L
L
Delgado
M
M
Ganea
D
D
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D006706:Homeostasis; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009479:Neuropeptides / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000502:physiology; D018005:Receptors, Vasoactive Intestinal Peptide / Q000502:physiology; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495402:Adcyap1 protein, mouse; C495504:Adcyap1r1 protein, mouse; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D016212:Transforming Growth Factor beta; C495507:Vipr1 protein, mouse; C495510:Vipr2 protein, mouse; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP