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G protein\u2010coupled receptor 4 (GPR4) has been proven to possess a broad range of physiological functions, but its function in synovial mast cells and RA is less reported. In this study, the protective effects of NE 52\u2010QQ57, a GPR4 antagonist, against interleukin\u00a0(IL)\u201033\u2010challenged inflammatory response in activated synovial mast cells were investigated. We report that IL\u201033 amplified GPR4 expression in HMC\u20101 mast cells. The GPR4 antagonist NE 52\u2010QQ57 alleviated IL\u201033\u2010caused secretions of IL\u201017, interferon\u2010\u03b3, and tumor necrosis factor\u2010\u03b1 in HMC\u20101 mast cells. Furthermore, we note that NE 52\u2010QQ57 reduced IL\u201033\u2010induced expressions of matrix metalloproteinase\u20102 (MMP\u20102) and MMP\u20109. Also, NE 52\u2010QQ57 inhibited cyclooxygenase 2\u00a0and prostaglandin E2 expression in IL\u201033\u2010challenged cells. Also, NE 52\u2010QQ57 ameliorated IL\u201033\u2010induced oxidative stress by reducing mitochondrial reactive oxygen species and 4\u2010hydroxynonenal. Mechanistically, NE 52\u2010QQ57 mitigated IL\u201033\u2010induced activation of the p38\/nuclear factor\u2010\u03baB\u00a0signaling pathway. We conclude that targeting GPR4 might be a promising strategy for RA treatment.<\/jats:p>","DOI":"10.1002\/jbt.23116","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T06:38:44Z","timestamp":1654583924000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The protective effects of NE 52\u2010QQ57 against interleukin\u201033\u2010induced inflammatory response in activated synovial mast cells"],"prefix":"10.1002","volume":"36","author":[{"given":"Jianqiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Emergency Surgery The First People's Hospital of Shangqiu City  Shangqiu Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency Surgery The First People's Hospital of Shangqiu City  Shangqiu Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6638-8798","authenticated-orcid":false,"given":"Zhijian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency Surgery The First People's Hospital of Shangqiu City  Shangqiu Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2013.06.029"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06075-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","unstructured":"K.Malm S.Bergman M.Andersson A.Bremander I.Larsson SAGE Open Med.2017 5 2050312117713647.","DOI":"10.1177\/2050312117713647"},{"key":"e_1_2_9_5_1","first-page":"924363","volume":"2013","author":"Duan L.","year":"2013","journal-title":"Clin. 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