Department of Health Sciences and Technology, Lee Gil Ya Cancer and Diabetes Institute, GAIHST, Gachon University, 155 Getbeolro, Yeonsu-gu, Incheon 21999, Republic of Korea.
Int J Mol Sci. 2023 Jun 28;24(13):10756. doi: 10.3390/ijms241310756.
Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-α, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA.
右美托咪定（Dex）具有镇痛、镇静和抗炎作用。虽然 Dex 对关节炎的作用已被揭示，但 Dex 与类风湿关节炎（RA）介导的炎症细胞因子相互作用的生理机制尚未得到充分研究。炎症和迁移的成纤维样滑膜细胞（FLS）参与了 RA 的严重程度。因此，我们旨在确定 Dex 对接受炎症细胞因子和生长因子等多种刺激输入的 RA-FLS 的影响。TNF-α、IL-6 和 EGF 等多种刺激输入增加了 RA-FLS 的 cAMP 浓度，而 Dex 处理则降低了 cAMP 浓度。Dex 降低了电中性钠-碳酸氢盐共转运蛋白 1（NBCn1）的表达、NBC 活性和随后的 RA-FLS 迁移。多种输入处理增强了 RA 相关因子（如炎症细胞因子和破骨细胞生成因子）的 mRNA 表达水平。值得注意的是，Dex 可有效降低 RA-FLS 中这些表达水平。这些结果表明，多种炎症或刺激输入增强了 RA-FLS 的迁移，而 Dex 的治疗缓解了激活的 RA-FLS，表明 Dex 是治疗 RA 的一种潜在治疗药物。
