Dexamethasone (Dex) exhibits broad-spectrum anti-inflammatory effects in chronic destructive rheumatoid arthritis. We present in vivo and in vitro evidence supporting the preventive effects and underlying mechanisms of Dex on collagen-induced arthritis (CIA)-induced synovial injuries. After successful induction of CIA, Wistar rats were administered Dex intraperitoneally (1 mg/kg) three times a week for more than 2 weeks. In vivo, paw swelling, arthritis scores, and histological evaluations were analyzed to determine the therapeutic effects of Dex on the progression of arthritis. In vitro, CIA fibroblast-like synoviocytes (FLSs) were treated for 48 h with vehicle (control group), 10 ng/mL IL-1α (IL-1α group), 10 ng/mL IL-1α + 10 μM Dex (Dex group), or 10 ng/mL IL-1α + 10 μg/mL anti-CD147 antibody (anti-CD147 group). Evaluations of FLSs proliferation, cell cycle, migration, gene expression of Cyclin D1, p27, p57, interleukin (IL)-1β, IL-6, IL-17, tumor necrosis factor (TNF)-α, CD147, CypB, matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13, ROS generation, protein expression of NF-κB and CD147, and translocation of NF-κB p65 were all conducted. The in vivo results showed that arthritis intensity was attenuated in the Dex-treated group. The in vitro findings demonstrated that treatment with Dex induced G0/G1 arrest and suppressed proliferation, migration, gene expression of IL-1β, IL-6, IL-17, TNF-α, CD147, CypB, MMP-3, MMP-9, and MMP-13, ROS generation and protein expression of NF-κB and CD147. Translocation of NF-κB p65 was inhibited by both Dex and anti-CD147 monoclonal antibody treatment. We offer molecular evidence of the anti-rheumatism efficacy Dex through hindrance to CD147, splendidly stabilization of the oxidative stress by downregulating the NF-κB signaling pathway.

地塞米松（Dex）在慢性破坏性类风湿关节炎中具有广谱抗炎作用。我们目前在体内和体外的证据支持Dex对胶原诱导的关节炎（CIA）引起的滑膜损伤的预防作用和潜在机制。成功诱导CIA后，每周两次腹腔注射Destar（1 mg / kg）Wistar大鼠，持续2周以上。在体内，分析爪子肿胀，关节炎评分和组织学评估以确定Dex对关节炎进展的治疗作用。在体外，用媒介物（对照组），10 ng / mLIL-1α（IL-1α组），10 ng / mLIL-1α+ 10μMDex（Dex）处理CIA成纤维样滑膜细胞（FLS）48小时组）或10 ng / mLIL-1α+ 10μg/ mL抗CD147抗体（抗CD147组）。评估FLS增殖，细胞周期，迁移，细胞周期蛋白D1，p27，p57，白介素（IL）-1β，IL-6，IL-17，肿瘤坏死因子（TNF）-α，CD147，CypB，基质金属蛋白酶的基因表达进行了-3（MMP-3），MMP-9和MMP-13，ROS的产生，NF-κB和CD147的蛋白表达以及NF-κBp65的易位。体内结果表明，Dex治疗组的关节炎强度​​减弱。体外研究结果表明，Dex治疗可诱导G0 / G1阻滞并抑制IL-1β，IL-6，IL-17，TNF-α，CD147，CypB，MMP-3，MMP-9的增殖，迁移，基因表达和MMP-13，ROS的产生以及NF-κB和CD147的蛋白表达。Dex和抗CD147单克隆抗体处理均抑制NF-κBp65的移位。