β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors

Human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet been investigated in ora...

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Main Authors: Giacomo Picciolo, Giovanni Pallio, Domenica Altavilla, Mario Vaccaro, Giacomo Oteri, Natasha Irrera, Francesco Squadrito
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/8/6/164
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author Giacomo Picciolo
Giovanni Pallio
Domenica Altavilla
Mario Vaccaro
Giacomo Oteri
Natasha Irrera
Francesco Squadrito
author_facet Giacomo Picciolo
Giovanni Pallio
Domenica Altavilla
Mario Vaccaro
Giacomo Oteri
Natasha Irrera
Francesco Squadrito
author_sort Giacomo Picciolo
collection DOAJ
description Human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet been investigated in oral mucositis. The aim of this study was to evaluate the therapeutic potential of β-Caryophyllene (BCP), a CB2 agonist, in an in vitro model of oral mucositis. GF and EC were stimulated with LPS (2 µg/mL) alone or in combination with BCP; a group of LPS challenged GF and EC were treated with BCP and AM630, a CB2 antagonist. LPS increased the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17A whereas it decreased the anti-inflammatory cytokine IL-13. The upstream signals were identified in an augmented expression of NF-κB and STAT-3 and in reduced mRNA levels of PPARγ and PGC-1α. BCP blunted the LPS-induced inflammatory phenotype and this effect was reverted by the CB2 antagonist AM630. These results suggest that CB2 receptors are an interesting target to develop innovative strategies for oral mucositis and point out that BCP exerts a marked curative effect in a preclinical model of oral mucositis which deserves to be confirmed in a clinical setting.
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spelling doaj.art-21029fd9885a49e1b37f3a63933a1f492023-11-20T04:03:12ZengMDPI AGBiomedicines2227-90592020-06-018616410.3390/biomedicines8060164β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 ReceptorsGiacomo Picciolo0Giovanni Pallio1Domenica Altavilla2Mario Vaccaro3Giacomo Oteri4Natasha Irrera5Francesco Squadrito6Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via C. Valeria, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, ItalyDepartment of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via C. Valeria, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, ItalyDepartment of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via C. Valeria, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, ItalyHuman gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet been investigated in oral mucositis. The aim of this study was to evaluate the therapeutic potential of β-Caryophyllene (BCP), a CB2 agonist, in an in vitro model of oral mucositis. GF and EC were stimulated with LPS (2 µg/mL) alone or in combination with BCP; a group of LPS challenged GF and EC were treated with BCP and AM630, a CB2 antagonist. LPS increased the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17A whereas it decreased the anti-inflammatory cytokine IL-13. The upstream signals were identified in an augmented expression of NF-κB and STAT-3 and in reduced mRNA levels of PPARγ and PGC-1α. BCP blunted the LPS-induced inflammatory phenotype and this effect was reverted by the CB2 antagonist AM630. These results suggest that CB2 receptors are an interesting target to develop innovative strategies for oral mucositis and point out that BCP exerts a marked curative effect in a preclinical model of oral mucositis which deserves to be confirmed in a clinical setting.https://www.mdpi.com/2227-9059/8/6/164β-CaryophylleneCB2 receptorsinflammationoral mucositisperiodontitis
spellingShingle Giacomo Picciolo
Giovanni Pallio
Domenica Altavilla
Mario Vaccaro
Giacomo Oteri
Natasha Irrera
Francesco Squadrito
β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors
Biomedicines
β-Caryophyllene
CB2 receptors
inflammation
oral mucositis
periodontitis
title β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors
title_full β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors
title_fullStr β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors
title_full_unstemmed β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors
title_short β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors
title_sort β caryophyllene reduces the inflammatory phenotype of periodontal cells by targeting cb2 receptors
topic β-Caryophyllene
CB2 receptors
inflammation
oral mucositis
periodontitis
url https://www.mdpi.com/2227-9059/8/6/164
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