Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis
PR domain-containing 1 with zinc finger domain (PRDM1) has been reported as a promoter of inflammation, which is a critical process involved in the pathogenesis of acute gouty arthritis. Herein, we sought to ascertain the function of PRDM1 in the development of acute gouty arthritis and related mech...
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| Format: | Article |
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Karger Publishers
2023-06-01
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| Series: | Journal of Innate Immunity |
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| Online Access: | https://beta.karger.com/Article/FullText/530966 |
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| author | Qingsong Zhao Nan Xia Jinmei Xu Yingnan Wang Luwen Feng Dihan Su Zhifeng Cheng |
| author_facet | Qingsong Zhao Nan Xia Jinmei Xu Yingnan Wang Luwen Feng Dihan Su Zhifeng Cheng |
| author_sort | Qingsong Zhao |
| collection | DOAJ |
| description | PR domain-containing 1 with zinc finger domain (PRDM1) has been reported as a promoter of inflammation, which is a critical process involved in the pathogenesis of acute gouty arthritis. Herein, we sought to ascertain the function of PRDM1 in the development of acute gouty arthritis and related mechanisms. At first, peripheral blood-derived monocytes from patients with acute gouty arthritis and healthy individuals were collected as experimental samples. Then, macrophages were induced from monocytes using phorbol myristate acetate (PMA). The expression patterns of PRDM1, sirtuin 2 (SIRT2), and NLR family, pyrin domain-containing 3 (NLRP3) were characterized by RT-qPCR and Western blot assay. PMA-induced macrophages were stimulated by monosodium urate (MSU) for in vitro experimentation. Meanwhile, a murine model of MSU-induced acute gouty arthritis was established for in vivo validation. PRDM1 was highly expressed while SIRT2 poorly expressed in patients with acute gouty arthritis. Loss of PRDM1 could reduce NLRP3 inflammasome and mature IL-1β levels and downregulate inflammatory cytokines in macrophages, which contributed to protection against acute gouty arthritis. Furthermore, results showed that PRDM1 could inhibit SIRT2 expression via binding to the deacetylase SIRT2 promoter. Finally, the in vivo experiments demonstrated that PRDM1 increased NLRP3 inflammasome and mature IL-1β through transcriptional inhibition of SIRT2, whereby aggravating MSU-induced acute gouty arthritis. To sum up, PRDM1 increased NLRP3 inflammasome through inhibiting SIRT2, consequently aggravating MSU-induced acute gouty arthritis. |
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| format | Article |
| id | doaj.art-79bac043b6bf4d5cbbf44422977f3aac |
| institution | Directory Open Access Journal |
| issn | 1662-8128 |
| language | English |
| last_indexed | 2024-03-12T21:36:31Z |
| publishDate | 2023-06-01 |
| publisher | Karger Publishers |
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| series | Journal of Innate Immunity |
| spelling | doaj.art-79bac043b6bf4d5cbbf44422977f3aac2023-07-27T06:18:22ZengKarger PublishersJournal of Innate Immunity1662-81282023-06-011110.1159/000530966530966Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty ArthritisQingsong Zhao0Nan Xia1Jinmei Xu2Yingnan Wang3Luwen Feng4Dihan Su5Zhifeng Cheng6Department of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaPR domain-containing 1 with zinc finger domain (PRDM1) has been reported as a promoter of inflammation, which is a critical process involved in the pathogenesis of acute gouty arthritis. Herein, we sought to ascertain the function of PRDM1 in the development of acute gouty arthritis and related mechanisms. At first, peripheral blood-derived monocytes from patients with acute gouty arthritis and healthy individuals were collected as experimental samples. Then, macrophages were induced from monocytes using phorbol myristate acetate (PMA). The expression patterns of PRDM1, sirtuin 2 (SIRT2), and NLR family, pyrin domain-containing 3 (NLRP3) were characterized by RT-qPCR and Western blot assay. PMA-induced macrophages were stimulated by monosodium urate (MSU) for in vitro experimentation. Meanwhile, a murine model of MSU-induced acute gouty arthritis was established for in vivo validation. PRDM1 was highly expressed while SIRT2 poorly expressed in patients with acute gouty arthritis. Loss of PRDM1 could reduce NLRP3 inflammasome and mature IL-1β levels and downregulate inflammatory cytokines in macrophages, which contributed to protection against acute gouty arthritis. Furthermore, results showed that PRDM1 could inhibit SIRT2 expression via binding to the deacetylase SIRT2 promoter. Finally, the in vivo experiments demonstrated that PRDM1 increased NLRP3 inflammasome and mature IL-1β through transcriptional inhibition of SIRT2, whereby aggravating MSU-induced acute gouty arthritis. To sum up, PRDM1 increased NLRP3 inflammasome through inhibiting SIRT2, consequently aggravating MSU-induced acute gouty arthritis.https://beta.karger.com/Article/FullText/530966inflammatory cytokinesmacrophagespyrin domain-containing 3nlr familyacetylated α-tubulinsirtuin 2pr domain-containing 1 with zinc finger domainacute gouty arthritis |
| spellingShingle | Qingsong Zhao Nan Xia Jinmei Xu Yingnan Wang Luwen Feng Dihan Su Zhifeng Cheng Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis Journal of Innate Immunity inflammatory cytokines macrophages pyrin domain-containing 3 nlr family acetylated α-tubulin sirtuin 2 pr domain-containing 1 with zinc finger domain acute gouty arthritis |
| title | Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis |
| title_full | Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis |
| title_fullStr | Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis |
| title_full_unstemmed | Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis |
| title_short | Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis |
| title_sort | pro inflammatory of prdm1 sirt2 nlrp3 axis in monosodium urate induced acute gouty arthritis |
| topic | inflammatory cytokines macrophages pyrin domain-containing 3 nlr family acetylated α-tubulin sirtuin 2 pr domain-containing 1 with zinc finger domain acute gouty arthritis |
| url | https://beta.karger.com/Article/FullText/530966 |
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