β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors

Natasha Irrera, Angela D’ascola, Giovanni Pallio, Alessandra Bitto, Emanuela Mazzon, Federica Mannino, Violetta Squadrito, Vincenzo Arcoraci, Letteria Minutoli, Giuseppe Maurizio Campo, Angela Avenoso, Elisa Benedetta Bongiorno, Mario Vaccaro, Francesco Squadrito, Domenica Altavilla

Research output: Contribution to journalArticlepeer-review

Abstract

β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 µg/100 µL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 µL) or its vehicle (100 µL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-kB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-kB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.

Original languageEnglish
Article number326
JournalBiomolecules
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 2019

Keywords

  • Arthritis
  • CAIA
  • CB2 receptors
  • PPAR-γ
  • β-caryophyllene

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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