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Inflammation Research

, Volume 65, Issue 11, pp 869–879 | Cite as

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

  • Magaiver Andrade-Silva
  • Luana Barbosa Correa
  • André Luis Peixoto Candéa
  • Simone C. Cavalher-Machado
  • Helene Santos Barbosa
  • Elaine Cruz Rosas
  • Maria G Henriques
Original Research Paper

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.

Keywords

CB2 receptor GP1a Neutrophil Mycobacteria Chemotaxis 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interests.

Supplementary material

11_2016_969_MOESM1_ESM.pdf (567 kb)
Supplementary material 1 (PDF 566 kb)
11_2016_969_MOESM2_ESM.pdf (367 kb)
Supplementary material 2 (PDF 367 kb)

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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Magaiver Andrade-Silva
    • 1
    • 3
  • Luana Barbosa Correa
    • 1
    • 3
  • André Luis Peixoto Candéa
    • 1
    • 3
  • Simone C. Cavalher-Machado
    • 1
  • Helene Santos Barbosa
    • 2
  • Elaine Cruz Rosas
    • 1
    • 3
  • Maria G Henriques
    • 1
    • 3
    • 4
  1. 1.Laboratório de Farmacologia Aplicada, Instituto de Tecnologia em Fármacos-FarmanguinhosFundação Oswaldo CruzRio de JaneiroBrasil
  2. 2.Laboratório de Biologia Estrutural, Instituto Oswaldo CruzFundação Oswaldo CruzRio de JaneiroBrasil
  3. 3.Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas (INCT-IDPN)Rio de JaneiroBrasil
  4. 4.Centro de Desenvolvimento Tecnológico em Saúde (CDTS)Rio de JaneiroBrasil

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