Department of Pediatrics, Division of Neonatology and Pediatric Hematology/Oncology, Chang Gung Memorial Hospital, Yunlin 638, Taiwan.
College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Cells. 2020 Jun 2;9(6):1378. doi: 10.3390/cells9061378.
Rheumatoid arthritis (RA) has been associated with air pollution, possibly due to the augmentation of inflammatory effects. In this study, we aimed to determine the roles of inflammatory pathways and microRNA involved in the pathogenesis of RA fibroblast-like synoviocytes (FLS) inflammation induced by particulate matter.
The inflammatory mediators, messenger RNAs, microRNAs and their interrelationships were investigated using western blotting, QPCR, ELISA and immunohistochemistry.
Particulate matter (PMs) induced an increase in the expression of interleukin-6 (IL-6) and cyclooxygenase-II (COX-II) in RA-FLS and microRNA-137 was found definitely to mediate the inflammatory pathways. PMs-induced generation of reactive oxygen species (ROS) in RA-FLS was attenuated by pretreatment with antioxidants. Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38 and JNK, followed by downregulation of microRNA-137. In vivo studies, the joints of rats exposed to PMs revealed synovial fibroblast inflammation under pathologic examination and the expressions of IL-6 and COX-II were obviously increased. PMs exposure results in activated ROS-mediated mitogen-activated protein kinase (MAPK) signaling pathways and cause increased IL-6 and COX-II through downregulation of hsa-miRNA-137, which lead to inflammation and RA exacerbation.
microRNA-137 plays an important role in PMs-induced RA acute exacerbation through MAPK signaling pathways and IL-6/COX-II activation. Targeting these mechanisms can potentially be used to develop new therapeutic strategies and prevention of RA inflammation in the future.
类风湿关节炎（RA）与空气污染有关，可能是由于炎症效应增强所致。在这项研究中，我们旨在确定参与 PM 诱导的 RA 成纤维样滑膜细胞（FLS）炎症发病机制的炎症途径和 microRNA 的作用。
使用 Western blot、QPCR、ELISA 和免疫组化研究了炎症介质、信使 RNA、microRNA 及其相互关系。
颗粒物（PMs）诱导 RA-FLS 中白细胞介素-6（IL-6）和环氧化酶-II（COX-II）的表达增加，并且 microRNA-137 被确定为介导炎症途径。用抗氧化剂预处理可减轻 PMs 诱导的 RA-FLS 中活性氧（ROS）的产生。Nox 依赖性 ROS 生成导致 ERK1/2、p38 和 JNK 的磷酸化，随后下调 microRNA-137。在体内研究中，暴露于 PMs 的大鼠关节在病理检查下显示滑膜成纤维细胞炎症，IL-6 和 COX-II 的表达明显增加。PMs 暴露导致 ROS 介导的丝裂原激活蛋白激酶（MAPK）信号通路激活，并通过下调 hsa-miRNA-137 导致 IL-6 和 COX-II 增加，从而导致炎症和 RA 恶化。
microRNA-137 通过 MAPK 信号通路和 IL-6/COX-II 激活在 PMs 诱导的 RA 急性加重中发挥重要作用。针对这些机制可能为未来开发 RA 炎症的新治疗策略和预防提供新的思路。
