1. Blockade of cannabinoid receptors reduces inflammation, leukocyte accumulation and neovascularization in a model of sponge-induced inflammatory angiogenesis
- Author
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Mauro M. Teixeira, Ariane C Gomes, Gabriel Augusto Oliveira Lopes, Remo Castro Russo, Lucíola S. Barcelos, Silvia Passos Andrade, Rodrigo Guabiraba, Mónica Amaral Ferreira, Amanda M. Coelho, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Universidade Federal de Minas Gerais, University of Glasgow, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil), Fundacao do Amparo a Pesquisas do Estado de Minas Gerais (FAPEMIG, Brazil), and Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)
- Subjects
Male ,medicine.medical_specialty ,Chemokine ,Cannabinoid receptor ,Angiogenesis ,Polyesters ,Immunology ,Polyurethanes ,chemokines ,Neovascularization ,Receptor, Cannabinoid, CB2 ,03 medical and health sciences ,cannabinoids ,angiogenesis ,Mice ,0302 clinical medicine ,Piperidines ,Receptor, Cannabinoid, CB1 ,Internal medicine ,Cannabinoid receptor type 2 ,medicine ,Leukocytes ,Animals ,Receptor ,Cannabinoid Receptor Antagonists ,030304 developmental biology ,Skin ,Pharmacology ,0303 health sciences ,Camphanes ,biology ,Neovascularization, Pathologic ,Chemistry ,Foreign-Body Reaction ,Foreign Bodies ,Endocannabinoid system ,3. Good health ,Mice, Inbred C57BL ,Endocrinology ,inflammation ,biology.protein ,Cannabinoid receptor antagonist ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Cytokines ,Pyrazoles ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,Rimonabant ,030217 neurology & neurosurgery - Abstract
Guabiraba, Rodrigo Russo, Remo C Coelho, Amanda M Ferreira, Monica A N D Lopes, Gabriel A O Gomes, Ariane K C Andrade, Silvia P Barcelos, Luciola S Teixeira, Mauro M Switzerland Inflamm Res. 2013 Aug;62(8):811-21. doi: 10.1007/s00011-013-0638-8. Epub 2013 May 31.; International audience; OBJECTIVE: Angiogenesis depends on a complex interaction between cellular networks and mediators. The endocannabinoid system and its receptors have been shown to play a role in models of inflammation. Here, we investigated whether blockade of cannabinoid receptors may interfere with inflammatory angiogenesis. MATERIALS AND METHODS: Polyester-polyurethane sponges were implanted in C57Bl/6j mice. Animals received doses (3 and 10 mg/kg/daily, s.c.) of the cannabinoid receptor antagonists SR141716A (CB1) or SR144528 (CB2). Implants were collected at days 7 and 14 for cytokines, hemoglobin, myeloperoxidase, and N-acetylglucosaminidase measurements, as indices of inflammation, angiogenesis, neutrophil and macrophage accumulation, respectively. Histological and morphometric analysis were also performed. RESULTS: Cannabinoid receptors expression in implants was detected from day 4 after implantation. Treatment with CB1 or CB2 receptor antagonists reduced cellular influx into sponges at days 7 and 14 after implantation, although CB1 receptor antagonist were more effective at blocking leukocyte accumulation. There was a reduction in TNF-alpha, VEGF, CXCL1/KC, CCL2/JE, and CCL3/MIP-1alpha levels, with increase in CCL5/RANTES. Both treatments reduced neovascularization. Dual blockade of cannabinoid receptors resulted in maximum inhibition of inflammatory angiogenesis. CONCLUSIONS: Blockade of cannabinoid receptors reduced leukocyte accumulation, inflammation and neovascularization, suggesting an important role of endocannabinoids in sponge-induced inflammatory angiogenesis both via CB1 and CB2 receptors.
- Published
- 2013
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