Liu Zhongbing, Sun Chi, Tao Ran, Xu Xinbao, Xu Libin, Cheng Hongbing, Wang Youhua, Zhang Dongmei
Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
Department of Orthopaedics, Traditional Chinese Medical Hospital of Nantong City, Nantong, 226001, China.
Inflammation. 2016 Feb;39(1):248-256. doi: 10.1007/s10753-015-0245-7.
Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient and antioxidant and has been reported to exert potent immunosuppressive effects. However, the therapeutically potential of PQQ on rheumatoid arthritis (RA) has not been explored. In the present study, the anti-inflammatory effects of PQQ were investigated in interleukin (IL)-1β-treated SW982 cells, a RA-like fibroblast-like synoviocytes (FLSs) injury model. Our observations showed that pretreatment with PQQ significantly inhibited the expression of matrix metalloproteinase (MMP)-1 and MMP-3 and suppressed the production of proinflammatory mediators such as TNF-α and IL-6 in IL-1β-treated SW982 cells. The nuclear translocation of nuclear factor kappa B (NF-κB) and the phosphorylation level of p65, p38, and JNK MAP kinase pathways were also inhibited by PQQ in IL-1β-stimulated SW982 cells. To further confirm the therapeutic effects of PQQ on RA in vivo, a collagen-induced arthritis (CIA) model was used. Mice treated with PQQ demonstrated marked attenuation of arthritic symptoms based on histopathology and clinical arthritis scores. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of RA.
吡咯喹啉醌（PQQ）是一种天然存在的氧化还原辅因子，作为一种必需营养素和抗氧化剂，据报道具有强大的免疫抑制作用。然而，PQQ对类风湿性关节炎（RA）的治疗潜力尚未得到探索。在本研究中，在白细胞介素（IL）-1β处理的SW982细胞（一种类风湿性关节炎样成纤维样滑膜细胞（FLSs）损伤模型）中研究了PQQ的抗炎作用。我们的观察结果表明，用PQQ预处理可显著抑制基质金属蛋白酶（MMP）-1和MMP-3的表达，并抑制IL-1β处理的SW982细胞中促炎介质如TNF-α和IL-6的产生。在IL-1β刺激的SW982细胞中，PQQ还抑制了核因子κB（NF-κB）的核转位以及p65、p38和JNK丝裂原活化蛋白激酶途径的磷酸化水平。为了进一步证实PQQ在体内对类风湿性关节炎的治疗作用，使用了胶原诱导的关节炎（CIA）模型。基于组织病理学和临床关节炎评分，用PQQ治疗的小鼠表现出关节炎症状的明显减轻。这些结果共同表明，PQQ可能是一种有前途的治疗药物，可以缓解类风湿性关节炎的进展。
