title: Netrin-1 signaling dampens inflammatory peritonitis.
abstract: Previous studies implicated the anti-inflammatory potential of the adenosine 2B receptor (A2BAR). A2BAR activation is achieved through adenosine, but this is limited by its very short t(1/2). To further define alternative adenosine signaling, we examined the role of netrin-1 during acute inflammatory peritonitis. In this article, we report that animals with endogenous repression of netrin-1 (Ntn1(+/-)) demonstrated increased cell count, increased peritoneal cytokine concentration, and pronounced histological changes compared with controls in a model of zymosan A peritonitis. Exogenous netrin-1 significantly decreased i.p. inflammatory changes. This effect was not present in animals with deletion of A2BAR (A2BAR(-/-)). A2BAR(-/-) animals demonstrated no change in cell count, i.p. cytokine concentration, or histology in response to netrin-1 injection. These data strengthen the role of netrin-1 as an immunomodulatory protein exerting its function in dependence of the A2BAR and further define alternative adenosine receptor signaling.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Eberhard-Karls University, Tübingen, Germany.
authors.forename: Valbona
authors.initials: V
authors.lastname: Mirakaj
authors.forename: Dimitra
authors.initials: D
authors.lastname: Gatidou
authors.forename: Claudia
authors.initials: C
authors.lastname: Pötzsch
authors.forename: Klemens
authors.initials: K
authors.lastname: König
authors.forename: Peter
authors.initials: P
authors.lastname: Rosenberger
mesh_terms: D000208:Acute Disease; D000818:Animals; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D000075388:Netrin-1; D010538:Peritonitis / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D043704:Receptor, Adenosine A2B / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*
chemical_list: D007155:Immunologic Factors; D018836:Inflammation Mediators; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D043704:Receptor, Adenosine A2B; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1