title: Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor.
abstract: Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor.
authors.affiliation: Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo, Av. Prof. Orlando Marques de Paiva, 87 - CEP 05508-270, Cidade Universitária, São Paulo, SP, Brazil.
authors.forename: Alison
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Viviane
authors.initials: V
authors.lastname: Ferraz-de-Paula
authors.forename: Milena L
authors.initials: ML
authors.lastname: Pinheiro
authors.forename: Luana B
authors.initials: LB
authors.lastname: Vitoretti
authors.forename: Domenica P
authors.initials: DP
authors.lastname: Mariano-Souza
authors.forename: Wanderley M
authors.initials: WM
authors.lastname: Quinteiro-Filho
authors.forename: Adriana T
authors.initials: AT
authors.lastname: Akamine
authors.forename: Vinícius I
authors.initials: VI
authors.lastname: Almeida
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Hallak
authors.forename: Antônio W
authors.initials: AW
authors.lastname: Zuardi
authors.forename: José A
authors.initials: JA
authors.lastname: Crippa
authors.forename: João
authors.initials: J
authors.lastname: Palermo-Neto
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002185:Cannabidiol / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000893:Anti-Inflammatory Agents; D002186:Cannabinoids; D018925:Chemokines; D016207:Cytokines; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D002185:Cannabidiol; D009195:Peroxidase