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AM404, paracetamol metabolite, prevents prostaglandin synthesis in activated microglia by inhibiting COX activity.
Saliba, Soraya Wilke; Marcotegui, Ariel R; Fortwängler, Ellen; Ditrich, Johannes; Perazzo, Juan Carlos; Muñoz, Eduardo; de Oliveira, Antônio Carlos Pinheiro; Fiebich, Bernd L.
Afiliação
  • Saliba SW; Department of Psychiatry and Psychotherapy, Laboratory of Translational Psychiatry, Faculty of Medicine, Medical Center - University of Freiburg, Hauptstr. 5, 79104, Freiburg, Germany. soraya.wilke.saliba@uniklinik-freiburg.de.
  • Marcotegui AR; Faculty of Biology, University of Freiburg, Freiburg, Germany. soraya.wilke.saliba@uniklinik-freiburg.de.
  • Fortwängler E; Laboratory of Hepatic Encephalopathy and Portal Hypertension, Center of Applied and Experimental Pathology, University of Buenos Aires, Buenos Aires, Argentina.
  • Ditrich J; Department of Psychiatry and Psychotherapy, Laboratory of Translational Psychiatry, Faculty of Medicine, Medical Center - University of Freiburg, Hauptstr. 5, 79104, Freiburg, Germany.
  • Perazzo JC; Department of Psychiatry and Psychotherapy, Laboratory of Translational Psychiatry, Faculty of Medicine, Medical Center - University of Freiburg, Hauptstr. 5, 79104, Freiburg, Germany.
  • Muñoz E; Laboratory of Hepatic Encephalopathy and Portal Hypertension, Center of Applied and Experimental Pathology, University of Buenos Aires, Buenos Aires, Argentina.
  • de Oliveira ACP; Departamento de Biología Celular, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofía, Fisiología e Inmunología, Universidad de Córdoba, Córdoba, Spain.
  • Fiebich BL; Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
J Neuroinflammation ; 14(1): 246, 2017 Dec 13.
Article em En | MEDLINE | ID: mdl-29237478
BACKGROUND: N-arachidonoylphenolamine (AM404), a paracetamol metabolite, is a potent agonist of the transient receptor potential vanilloid type 1 (TRPV1) and low-affinity ligand of the cannabinoid receptor type 1 (CB1). There is evidence that AM404 exerts its pharmacological effects in immune cells. However, the effect of AM404 on the production of inflammatory mediators of the arachidonic acid pathway in activated microglia is still not fully elucidated. METHOD: In the present study, we investigated the effects of AM404 on the eicosanoid production induced by lipopolysaccharide (LPS) in organotypic hippocampal slices culture (OHSC) and primary microglia cultures using Western blot, immunohistochemistry, and ELISA. RESULTS: Our results show that AM404 inhibited LPS-mediated prostaglandin E2 (PGE2) production in OHSC, and LPS-stimulated PGE2 release was totally abolished in OHSC if microglial cells were removed. In primary microglia cultures, AM404 led to a significant dose-dependent decrease in the release of PGE2, independent of TRPV1 or CB1 receptors. Moreover, AM404 also inhibited the production of PGD2 and the formation of reactive oxygen species (8-iso-PGF2 alpha) with a reversible reduction of COX-1- and COX-2 activity. Also, it slightly decreased the levels of LPS-induced COX-2 protein, although no effect was observed on LPS-induced mPGES-1 protein synthesis. CONCLUSIONS: This study provides new significant insights about the potential anti-inflammatory role of AM404 and new mechanisms of action of paracetamol on the modulation of prostaglandin production by activated microglia.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Prostaglandinas / Ácidos Araquidônicos / Microglia / Anti-Inflamatórios Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Prostaglandinas / Ácidos Araquidônicos / Microglia / Anti-Inflamatórios Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article