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Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose\u2010dependently inhibits tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) and interleukin (IL)\u20101\u03b2 expression through the PI3K\/AKT, ERK, and NF\u2010\u03baB signaling pathways. We also identified that melatonin inhibits TNF\u2010\u03b1 and IL\u20101\u03b2 production by upregulating miR\u20103150a\u20103p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast\u2010like synoviocytes confirmed that the MT1 receptor is needed for the anti\u2010inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen\u2010induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF\u2010\u03b1 and IL\u20101\u03b2 production through downregulation of the PI3K\/AKT, ERK, NF\u2010\u03baB signaling pathways, as well as miR\u20103150a\u20103p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.<\/jats:p>","DOI":"10.1111\/jpi.12560","type":"journal-article","created":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T10:48:27Z","timestamp":1547635707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":143,"title":["Melatonin attenuates TNF\u2010\u03b1 and IL\u20101\u03b2 expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis"],"prefix":"10.1111","volume":"66","author":[{"given":"Chien\u2010Chung","family":"Huang","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medical Science China Medical University Taichung Taiwan"},{"name":"Division of Immunology and Rheumatology, Department of Internal Medicine China Medical University Hospital Taichung 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