Picciolo Giacomo, Pallio Giovanni, Altavilla Domenica, Vaccaro Mario, Oteri Giacomo, Irrera Natasha, Squadrito Francesco
Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via C. Valeria, 98125 Messina, Italy.
Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy.
Biomedicines. 2020 Jun 17;8(6):164. doi: 10.3390/biomedicines8060164.
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.
具有炎症表型的人牙龈成纤维细胞（GF）和人口腔黏膜上皮细胞（EC）是探索用于口腔黏膜炎的药物治疗活性的宝贵实验范例。大麻素受体2（CB2）在口腔黏膜炎中的作用尚未得到研究。本研究的目的是评估CB2激动剂β-石竹烯（BCP）在口腔黏膜炎体外模型中的治疗潜力。单独用脂多糖（LPS，2µg/mL）或与BCP联合刺激GF和EC；一组经LPS刺激的GF和EC用BCP和CB2拮抗剂AM630处理。LPS增加了炎性细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和白细胞介素-17A（IL-17A），而降低了抗炎细胞因子白细胞介素-13（IL-13）。上游信号表现为核因子-κB（NF-κB）和信号转导子与转录激活子3（STAT-3）表达增加，过氧化物酶体增殖物激活受体γ（PPARγ）和过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）的mRNA水平降低。BCP减弱了LPS诱导的炎症表型，且这种作用被CB2拮抗剂AM630逆转。这些结果表明，CB2受体是开发口腔黏膜炎创新治疗策略的一个有意义的靶点，并指出BCP在口腔黏膜炎临床前模型中具有显著的治疗效果，这值得在临床环境中得到证实。
