Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis

Abstract We previously reported that synovial mast cells (MCs) from patients with rheumatoid arthritis (RA) produced TNF-α in response to immune complexes via FcγRI and FcγRIIA. However, the specific functions of synovial MCs in RA remain unclear. This study aimed to elucidate those functions. Synov...

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Autores principales:	Shintaro Mishima, Jun-ichi Kashiwakura, Shota Toyoshima, Tomomi Sasaki-Sakamoto, Yutaka Sano, Kazuyoshi Nakanishi, Kenji Matsumoto, Yoshimichi Okayama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f5b5fbc6f1e848db976dde89bfbb4662
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spelling	oai:doaj.org-article:f5b5fbc6f1e848db976dde89bfbb46622021-12-02T15:52:58ZHigher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis10.1038/s41598-021-84963-72045-2322https://doaj.org/article/f5b5fbc6f1e848db976dde89bfbb46622021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84963-7https://doaj.org/toc/2045-2322Abstract We previously reported that synovial mast cells (MCs) from patients with rheumatoid arthritis (RA) produced TNF-α in response to immune complexes via FcγRI and FcγRIIA. However, the specific functions of synovial MCs in RA remain unclear. This study aimed to elucidate those functions. Synovial tissues and fluid were obtained from RA and osteoarthritis (OA) patients undergoing joint replacement surgery. Synovium-derived, cultured MCs were generated by culturing dispersed synovial cells with stem cell factor. We performed microarray-based screening of mRNA and microRNA (miRNA), followed by quantitative RT-PCR-based verification. Synovial MCs from RA patients showed significantly higher prostaglandin systhetase (PTGS)1 and PTGS2 expression compared with OA patients’ MCs, and they produced significantly more prostaglandin D2 (PGD2) following aggregation of FcγRI. PGD2 induced IL-8 production by human group 2 innate lymphoid cells, suggesting that PGD2-producing MCs induce neutrophil recruitment into the synovium of RA patients. PTGS2 mRNA expression in RA patients’ MCs correlated inversely with miRNA-199a-3p expression, which down-regulated PTGS2. RA patients’ synovial fluid contained significantly more PGD2 compared with OA patients’ fluid. Synovial MCs might regulate inflammation in RA through hyper-production of PGD2 following FcRγ aggregation. Our findings indicate functional heterogeneity of human MCs among diseases.Shintaro MishimaJun-ichi KashiwakuraShota ToyoshimaTomomi Sasaki-SakamotoYutaka SanoKazuyoshi NakanishiKenji MatsumotoYoshimichi OkayamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shintaro Mishima Jun-ichi Kashiwakura Shota Toyoshima Tomomi Sasaki-Sakamoto Yutaka Sano Kazuyoshi Nakanishi Kenji Matsumoto Yoshimichi Okayama Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis
description	Abstract We previously reported that synovial mast cells (MCs) from patients with rheumatoid arthritis (RA) produced TNF-α in response to immune complexes via FcγRI and FcγRIIA. However, the specific functions of synovial MCs in RA remain unclear. This study aimed to elucidate those functions. Synovial tissues and fluid were obtained from RA and osteoarthritis (OA) patients undergoing joint replacement surgery. Synovium-derived, cultured MCs were generated by culturing dispersed synovial cells with stem cell factor. We performed microarray-based screening of mRNA and microRNA (miRNA), followed by quantitative RT-PCR-based verification. Synovial MCs from RA patients showed significantly higher prostaglandin systhetase (PTGS)1 and PTGS2 expression compared with OA patients’ MCs, and they produced significantly more prostaglandin D2 (PGD2) following aggregation of FcγRI. PGD2 induced IL-8 production by human group 2 innate lymphoid cells, suggesting that PGD2-producing MCs induce neutrophil recruitment into the synovium of RA patients. PTGS2 mRNA expression in RA patients’ MCs correlated inversely with miRNA-199a-3p expression, which down-regulated PTGS2. RA patients’ synovial fluid contained significantly more PGD2 compared with OA patients’ fluid. Synovial MCs might regulate inflammation in RA through hyper-production of PGD2 following FcRγ aggregation. Our findings indicate functional heterogeneity of human MCs among diseases.
format	article
author	Shintaro Mishima Jun-ichi Kashiwakura Shota Toyoshima Tomomi Sasaki-Sakamoto Yutaka Sano Kazuyoshi Nakanishi Kenji Matsumoto Yoshimichi Okayama
author_facet	Shintaro Mishima Jun-ichi Kashiwakura Shota Toyoshima Tomomi Sasaki-Sakamoto Yutaka Sano Kazuyoshi Nakanishi Kenji Matsumoto Yoshimichi Okayama
author_sort	Shintaro Mishima
title	Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis
title_short	Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis
title_full	Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis
title_fullStr	Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis
title_full_unstemmed	Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis
title_sort	higher pgd2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via mir-199a-3p/prostaglandin synthetase 2 axis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f5b5fbc6f1e848db976dde89bfbb4662
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Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis

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