@article{oai:repository.lib.tottori-u.ac.jp:00004639, author = {Sueda, Yuriko and 岡崎, 亮太 and Okazaki, Ryota and 舟木, 佳弘 and Funaki, Yoshihiro and 長谷川, 泰之 and 原田, 智也 and Harada, Tomoya and 高田, 美樹 and Takata, Miki and 森田, 正人 and Morita, Masato and 山崎, 章 and Yamasaki, Akira and Sueda, Yuriko and Hasegawa, Yasuyuki and Ishikawa, Hiroki and Hirayama, Yuki and Inui, Genki}, issue = {2}, journal = {Yonago Acta Medica, Yonago Acta Medica}, month = {May}, note = {Background : Tumor necrosis factor (TNF)-α, a proinflammatory cytokine, is involved in the pathogenesis of rheumatoid arthritis (RA). The omega-3 unsaturated fatty acid-derived metabolites resolvin (Rv) D1, RvE1, and maresin-1 (MaR1) have been reported as anti-inflammatory lipid mediators and are known as specialized pro-resolving mediators (SPMs). In this study, we aimed to investigate the anti-inflammatory effects of SPMs on TNF-α-induced responses in synovial fibroblasts. Methods: We investigated the effects of SPMs on gene expression and/or production of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), interleukin (IL)-6, and matrix metalloproteinase (MMP)-3, which are involved in TNF-α-induced synovitis in RA or OA synovial fibroblasts, by quantitative real-time PCR. We also investigated the effects of SPMs on the mitogen-activated protein kinase (MAPK) signaling pathway by western blotting. Anti-inflammatory effects of SPMs were evaluated by applying SPMs to cultured synovial fibroblasts, followed by TNF-α stimulation. Results: The induction of COX-2, mPGES-1, IL-6, and MMP-3 by TNF-α in synovial fibroblasts was not suppressed by omega 3-derived SPMs regardless of their origin such as RA or OA. SPMs had no effect on lipid mediator receptor gene expression induce by TNF-α and did not inhibit the TNF-α-activated MAPK signaling pathway. The production of COX-2 and IL-6 protein was significantly decreased by p38 inhibitor. Conclusion: Despite reports on the anti-inflammatory effect of omega 3-derived SPMs, its anti-inflammatory effect on TNF-α-induced responses was not observed in synovial fibroblasts. The reason may be that SPMs have no suppressive effect on p38 activation, which plays an important role in the production of inflammatory cytokines in synovial fibroblasts.}, pages = {111--125}, title = {Specialized Pro-Resolving Mediators Do Not Inhibit the Synthesis of Inflammatory Mediators Induced by Tumor Necrosis Factor-α in Synovial Fibroblasts}, volume = {65}, year = {2022}, yomi = {スエダ, ユリコ and オカザキ, リョウタ and フナキ, ヨシヒロ and ハセガワ, ヤスユキ and ハラダ, トモヤ and タカタ, ミキ and モリタ, マサト and ヤマサキ, アキラ and スエダ, ユリコ and ハセガワ, ヤスユキ} }