{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T14:51:46Z","timestamp":1775832706297,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T00:00:00Z","timestamp":1591056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012283","name":"Chiayi Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPGMF0033"],"award-info":[{"award-number":["CMRPGMF0033"]}],"id":[{"id":"10.13039\/501100012283","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: 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. Methods: The inflammatory mediators, messenger RNAs, microRNAs and their interrelationships were investigated using western blotting, QPCR, ELISA and immunohistochemistry. Results: 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. Conclusions: 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.<\/jats:p>","DOI":"10.3390\/cells9061378","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T09:19:27Z","timestamp":1591089567000},"page":"1378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Urban Particulate Matter Enhances ROS\/IL-6\/COX-II Production by Inhibiting MicroRNA-137 in Synovial Fibroblast of Rheumatoid Arthritis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0343-2370","authenticated-orcid":false,"given":"Ming-Horng","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology and Pediatric Hematology\/Oncology, Chang Gung Memorial Hospital, Yunlin 638, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao-Ching","family":"Chi","sequence":"additional","affiliation":[{"name":"Chronic Disease and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, Chiayi County 613, Taiwan"},{"name":"Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Puzi City, Chiayi County 613, Taiwan"},{"name":"Department of Respiratory Care, Chang Gung University of Science and Technology, Puzi City, Chiayi County 613, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0798-5378","authenticated-orcid":false,"given":"Jen-Fu","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, Chang Gung Memorial Hospital, Lin-Kou, New Taipei City 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I-Ta","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei City 111, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ko-Ming","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Puzi City, Chiayi County 613, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Ling","family":"Fang","sequence":"additional","affiliation":[{"name":"Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung 83347, Taiwan"},{"name":"Super Micro Research and Technology Center, Cheng Shiu University, Kaohsiung 83347, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5341-7764","authenticated-orcid":false,"given":"Ming-Hsueh","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiang-Wen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County 61363, Taiwan"},{"name":"Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, Chiayi County 61363, Taiwan"},{"name":"Department of Safety Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan"},{"name":"College of Medicine, Chang Gung University, Guishan Dist, Taoyuan City 33303, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju-Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei City 11101, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan"},{"name":"School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrrheum.2012.190","article-title":"Duality of fibroblast-like synoviocytes in RA: Passive responders and imprinted aggressors","volume":"9","author":"Bottini","year":"2013","journal-title":"Nat. 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