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

Abstract

Objective and design

β-Caryophyllene (BCP) is a sesquiterpene that binds to the cannabinoid 2 (CB2) receptor and exerts anti-inflammatory effects. In this study, we investigated the anti-inflammatory effect of BCP and another CB2 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 CB2 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 B4 (LTB4), IL-12, and nitric oxide production. GP1a had a similar effect to BCP. Preincubation of neutrophils with BCP (10 µM) impaired chemotaxis toward LTB4 and adhesion to endothelial cells stimulated with TNF-α, and both, BCP and GP1a, impaired LTB4-induced actin polymerization.

Conclusion

These results suggest that the CB2 receptor may represent a new target for modulating the inflammatory reaction induced by mycobacteria.

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Acknowledgments

This work was supported by the Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) Sediadas 32/2013), Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq) 305986/2014-7 and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) PROCAD 149/2007. M. A. Silva and L. B. Correa are students of the Programa de Pós-Graduação em Biologia Celular e Molecular from Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.

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Correspondence to Maria G Henriques.

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Responsible Editor: John Di Battista.

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Andrade-Silva, M., Correa, L.B., Candéa, A.L.P. et al. The cannabinoid 2 receptor agonist β-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration. Inflamm. Res. 65, 869–879 (2016). https://doi.org/10.1007/s00011-016-0969-3

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Keywords

  • CB2 receptor
  • GP1a
  • Neutrophil
  • Mycobacteria
  • Chemotaxis