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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Nature Portfolio
2021-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-84963-7 |
| _version_ | 1818347107222814720 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T17:28:54Z |
| format | Article |
| id | doaj.art-f5b5fbc6f1e848db976dde89bfbb4662 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T17:28:54Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f5b5fbc6f1e848db976dde89bfbb46622022-12-21T23:37:06ZengNature PortfolioScientific Reports2045-23222021-03-0111111410.1038/s41598-021-84963-7Higher PGD2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axisShintaro Mishima0Jun-ichi Kashiwakura1Shota Toyoshima2Tomomi Sasaki-Sakamoto3Yutaka Sano4Kazuyoshi Nakanishi5Kenji Matsumoto6Yoshimichi Okayama7Allergy and Immunology Research Project Team, Nihon University School of MedicineAllergy and Immunology Research Project Team, Nihon University School of MedicineAllergy and Immunology Research Project Team, Nihon University School of MedicineAllergy and Immunology Research Project Team, Nihon University School of MedicineAllergy and Immunology Research Project Team, Nihon University School of MedicineDepartment of Orthopaedic Surgery, Nihon University School of MedicineDepartment of Allergy and Clinical Immunology, National Research Institute for Child Health and DevelopmentAllergy and Immunology Research Project Team, Nihon University School of MedicineAbstract 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.https://doi.org/10.1038/s41598-021-84963-7 |
| spellingShingle | 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 Scientific Reports |
| 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_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_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_sort | higher pgd2 production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via mir 199a 3p prostaglandin synthetase 2 axis |
| url | https://doi.org/10.1038/s41598-021-84963-7 |
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