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

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 charac...

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Autores principales: Irrera, Natasha, D’Ascola, Angela, Pallio, Giovanni, Bitto, Alessandra, Mazzon, Emanuela, Mannino, Federica, Squadrito, Violetta, Arcoraci, Vincenzo, Minutoli, Letteria, Campo, Giuseppe Maurizio, Avenoso, Angela, Bongiorno, Elisa Benedetta, Vaccaro, Mario, Squadrito, Francesco, Altavilla, Domenica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723248/
https://www.ncbi.nlm.nih.gov/pubmed/31370242
http://dx.doi.org/10.3390/biom9080326
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author Irrera, Natasha
D’Ascola, Angela
Pallio, Giovanni
Bitto, Alessandra
Mazzon, Emanuela
Mannino, Federica
Squadrito, Violetta
Arcoraci, Vincenzo
Minutoli, Letteria
Campo, Giuseppe Maurizio
Avenoso, Angela
Bongiorno, Elisa Benedetta
Vaccaro, Mario
Squadrito, Francesco
Altavilla, Domenica
author_facet Irrera, Natasha
D’Ascola, Angela
Pallio, Giovanni
Bitto, Alessandra
Mazzon, Emanuela
Mannino, Federica
Squadrito, Violetta
Arcoraci, Vincenzo
Minutoli, Letteria
Campo, Giuseppe Maurizio
Avenoso, Angela
Bongiorno, Elisa Benedetta
Vaccaro, Mario
Squadrito, Francesco
Altavilla, Domenica
author_sort Irrera, Natasha
collection PubMed
description 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-ĸB 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-ĸB 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.
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spelling pubmed-67232482019-09-10 β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors Irrera, Natasha D’Ascola, Angela Pallio, Giovanni Bitto, Alessandra Mazzon, Emanuela Mannino, Federica Squadrito, Violetta Arcoraci, Vincenzo Minutoli, Letteria Campo, Giuseppe Maurizio Avenoso, Angela Bongiorno, Elisa Benedetta Vaccaro, Mario Squadrito, Francesco Altavilla, Domenica Biomolecules Article 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-ĸB 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-ĸB 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. MDPI 2019-07-31 /pmc/articles/PMC6723248/ /pubmed/31370242 http://dx.doi.org/10.3390/biom9080326 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Irrera, Natasha
D’Ascola, Angela
Pallio, Giovanni
Bitto, Alessandra
Mazzon, Emanuela
Mannino, Federica
Squadrito, Violetta
Arcoraci, Vincenzo
Minutoli, Letteria
Campo, Giuseppe Maurizio
Avenoso, Angela
Bongiorno, Elisa Benedetta
Vaccaro, Mario
Squadrito, Francesco
Altavilla, Domenica
β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors
title β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors
title_full β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors
title_fullStr β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors
title_full_unstemmed β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors
title_short β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors
title_sort β-caryophyllene mitigates collagen antibody induced arthritis (caia) in mice through a cross-talk between cb2 and ppar-γ receptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723248/
https://www.ncbi.nlm.nih.gov/pubmed/31370242
http://dx.doi.org/10.3390/biom9080326
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