Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, China.
Department of Stomatology, 74753Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221099598. doi: 10.1177/09603271221099598.
Pulpitis is a common oral inflammatory disease in dental pulp commonly associated with bacterial infection. G protein-coupled receptor 55 (GPR55) is a member of the G protein-coupled receptors family that has been found to regulate inflammatory response. However, its roles in dental pulp inflammation have not been investigated. In this study, we used lipopolysaccharide (LPS) to induce inflammation in human dental pulp cells (hDPCs) to simulate an in vitro model of pulpitis. We found that LPS markedly induced the GPR55 expression in hDPCs. Treatment with the GPR55 antagonist ML-193 ameliorated the LPS-caused decrease in cell viability and increase in lactate dehydrogenase release. The upregulated inflammatory cytokines, interleukin-6 (IL-6) and tumour necrosis factor α, in LPS-challenged hDPCs were also attenuated by ML-193. Treatment with ML-193 ameliorated LPS-induced production of the inflammatory mediators cyclooxygenase-2/prostaglandin E2 (COX-2/PGE), and inducible nitric oxide synthase/nitric oxide (iNOS/NO) in hDPCs. ML-193 also inhibited the activation of Toll-like receptor 4-myeloid differentiation primary response 88-nuclear factor-κB (TLR4-Myd88-NF-κB) signaling in LPS-induced hDPCs via decreased expressions of TLR4, Myd88, and p-NF-κB 65. Our study provides evidence that the GPR55 antagonist ML-193 exhibited anti-inflammatory activity in LPS-stimulated hDPCs through inhibiting TLR4-Myd88-NF-κB signaling. The results imply that ML-193 might be a novel agent for pulpitis.
牙髓炎是一种常见的口腔炎性疾病，常与细菌感染有关。G 蛋白偶联受体 55（GPR55）是 G 蛋白偶联受体家族的一员，已被发现可调节炎症反应。然而，其在牙髓炎症中的作用尚未得到研究。在本研究中，我们使用脂多糖（LPS）诱导人牙髓细胞（hDPC）炎症，模拟牙髓炎的体外模型。我们发现 LPS 显著诱导 hDPC 中 GPR55 的表达。用 GPR55 拮抗剂 ML-193 处理可改善 LPS 引起的细胞活力下降和乳酸脱氢酶释放增加。LPS 刺激的 hDPC 中上调的炎症细胞因子白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）也被 ML-193 减弱。ML-193 可改善 LPS 诱导的 hDPC 中炎症介质环加氧酶 2/前列腺素 E2（COX-2/PGE）和诱导型一氧化氮合酶/一氧化氮（iNOS/NO）的产生。ML-193 还通过降低 TLR4、Myd88 和 p-NF-κB65 的表达，抑制 LPS 诱导的 hDPC 中 Toll 样受体 4-髓样分化初级反应 88-核因子-κB（TLR4-Myd88-NF-κB）信号的激活。本研究提供的证据表明，GPR55 拮抗剂 ML-193 通过抑制 TLR4-Myd88-NF-κB 信号通路在 LPS 刺激的 hDPC 中表现出抗炎活性。结果表明，ML-193 可能是一种新的牙髓炎治疗药物。
