title: Anti-inflammatory role in septic shock of pituitary adenylate cyclase-activating polypeptide receptor.
abstract: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two mediators synthesized by immune cells, specially under inflammatory and antigen stimulation conditions. Reports have shown that neuropeptides attenuate the deleterious consequences of septic shock both by down-regulating the production of proinflammatory mediators and by stimulating the production of anti-inflammatory cytokines by activated macrophages. In this study, we used a knockout for the PACAP receptor (PAC1(-/-)) to demonstrate an important protective role for PAC1 receptor in endotoxic shock. Moreover, our results indicate that PAC1 receptor acts in vivo as an anti-inflammatory receptor, at least in part, by attenuating lipopolysaccharide (LPS)-induced production of proinflammatory IL-6, which appears to be the main cytokine regulating the expression of the majority of the acute phase protein genes, which are an important deleterious component of septic shock. Besides, our findings point to endogenously produced VIP and PACAP as participants of the natural anti-inflammatory machinery. Because VIP and PACAP are two attractive candidates for the development of therapies against acute and chronic inflammatory diseases, septic shock, and autoimmune diseases, this paper represents a contribution to the understanding of the mechanism of action of these anti-inflammatory agents.
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University, 28040 Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martinez
authors.forename: Catalina
authors.initials: C
authors.lastname: Abad
authors.forename: Mario
authors.initials: M
authors.lastname: Delgado
authors.forename: Alicia
authors.initials: A
authors.lastname: Arranz
authors.forename: Maria G
authors.initials: MG
authors.lastname: Juarranz
authors.forename: Nieves
authors.initials: N
authors.lastname: Rodriguez-Henche
authors.forename: Philippe
authors.initials: P
authors.lastname: Brabet
authors.forename: Javier
authors.initials: J
authors.lastname: Leceta
authors.forename: Rosa P
authors.initials: RP
authors.lastname: Gomariz
mesh_terms: D000818:Animals; D005260:Female; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012772:Shock, Septic / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: C495504:Adcyap1r1 protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D014409:Tumor Necrosis Factor-alpha; D014660:Vasoactive Intestinal Peptide