The cannabinoid 2 receptor agonist β-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration

• Published in: Inflammation research Vol. 65; no. 11; pp. 869 - 879
• Main Authors: Andrade-Silva, Magaiver, Correa, Luana Barbosa, Candéa, André Luis Peixoto, Cavalher-Machado, Simone C., Barbosa, Helene Santos, Rosas, Elaine Cruz, Henriques, Maria G
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.11.2016
• Subjects: Actins - metabolism; Allergology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cell Adhesion - drug effects; Cell Line; Cell Movement - drug effects; Cytokines - immunology; Dermatology; Dinoprostone - metabolism; Immunology; Macrophages - drug effects; Male; Mice, Inbred C57BL; Mycobacterium bovis; Neurology; Neutrophils - drug effects; Neutrophils - metabolism; Neutrophils - physiology; Nitric Oxide - metabolism; Original Research Paper; Pharmacology/Toxicology; Pleurisy - drug therapy; Pleurisy - immunology; Pneumonia - drug therapy; Pneumonia - immunology; Receptor, Cannabinoid, CB2 - agonists; Rheumatology; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - immunology; GP1a; receptor; Neutrophil; Chemotaxis; Mycobacteria; CB; CB2 receptor
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-016-0969-3

Objective and design β-Caryophyllene (BCP) is a sesquiterpene that binds to the cannabinoid 2 (CB 2 ) receptor and exerts anti-inflammatory effects. In this study, we investigated the anti-inflammatory effect of BCP and another CB 2 agonist, GP1a in inflammatory experimental model induced by Mycobacterium bovis (BCG). Methods C57Bl/6 mice were pretreated orally with BCP (0.5–50 mg/kg) or intraperitonealy with GP1a (10 mg/kg) 1 h before the induction of pleurisy or pulmonary inflammation by BCG. The direct action of CB 2 agonists on neutrophils function was evaluated in vitro. Results β-Caryophyllene (50 mg/kg) impaired BCG-induced neutrophil accumulation in pleurisy without affecting mononuclear cells or the production of TNF-α and CCL2/MCP-1. However, BCP inhibited CXCL1/KC, leukotriene B 4 (LTB 4 ), IL-12, and nitric oxide production. GP1a had a similar effect to BCP. Preincubation of neutrophils with BCP (10 µM) impaired chemotaxis toward LTB 4 and adhesion to endothelial cells stimulated with TNF-α, and both, BCP and GP1a, impaired LTB 4 -induced actin polymerization. Conclusion These results suggest that the CB 2 receptor may represent a new target for modulating the inflammatory reaction induced by mycobacteria.