PMID- 37996809 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20231127 IS - 1528-3658 (Electronic) IS - 1076-1551 (Print) IS - 1076-1551 (Linking) VI - 29 IP - 1 DP - 2023 Nov 23 TI - Maresin1 ameliorates MSU crystal-induced inflammation by upregulating Prdx5 expression. PG - 158 LID - 10.1186/s10020-023-00756-w [doi] LID - 158 AB - BACKGROUND: Maresin1 (MaR1) is a potent lipid mediator that exhibits significant anti-inflammatory activity in the context of several inflammatory diseases. A previous study reported that MaR1 could suppress MSU crystal-induced peritonitis in mice. To date, the molecular mechanism by which MaR1 inhibits MSU crystal-induced inflammation remains poorly understood. METHODS: Mousebone marrow-derived macrophages (BMDMs) were pretreated with MaR1 and then stimulated with FAs (palmitic, C16:0 and stearic, C18:0) plus MSU crystals (FAs + MSUc). In vivo, the effects of MaR1 treatment or Prdx5 deficiency on MSUc induced peritonitis and arthritis mouse models were evaluated. RESULTS: The current study indicated that MaR1 effectively suppressed MSUc induced inflammation in vitro and in vivo. MaR1 reversed the decrease in Prdx5 mRNA and protein levels induced by FAs + MSUc. Further assays demonstrated that MaR1 acceleratedPrdx5 expression by regulating the Keap1-Nrf2 signaling axis. Activation of AMPK by Prdx5 improved homeostasis of the TXNIP and TRX proteins and alleviated mitochondrial fragmentation. In addition, Prdx5 overexpression inhibited the expression of CPT1A, a key enzyme for fatty acid oxidation (FAO). Prdx5 protected against defects in FA + MSUc induced FAO and the urea cycle. CONCLUSION: MaR1 treatment effectively attenuated MSUc induced inflammation by upregulating Prdx5 expression. Our study provides a new strategy by which Prdx5 may help prevent acute gout attacks. CI - (c) 2023. The Author(s). FAU - Jiang, Hui AU - Jiang H AD - Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan Province, China. AD - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, 234# Fujiang Road, Nanchong, 637001, Sichuan Province, China. FAU - Song, DianZe AU - Song D AD - Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan Province, China. AD - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, 234# Fujiang Road, Nanchong, 637001, Sichuan Province, China. AD - Medical Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan, China. FAU - Zhou, Xiaoqin AU - Zhou X AD - Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan Province, China. AD - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, 234# Fujiang Road, Nanchong, 637001, Sichuan Province, China. FAU - Chen, Feng AU - Chen F AD - Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan Province, China. AD - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, 234# Fujiang Road, Nanchong, 637001, Sichuan Province, China. FAU - Yu, Qingqing AU - Yu Q AD - Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan Province, China. AD - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, 234# Fujiang Road, Nanchong, 637001, Sichuan Province, China. AD - Medical Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan, China. FAU - Ren, Long AU - Ren L AD - The Fifth People's Hospital of Nanchong City, 21# Bajiao Street, Nanchong, 637100, Sichuan, China. FAU - Dai, Qian AU - Dai Q AD - Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan Province, China. AD - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, 234# Fujiang Road, Nanchong, 637001, Sichuan Province, China. FAU - Zeng, Mei AU - Zeng M AUID- ORCID: 0000-0002-5661-7101 AD - Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan Province, China. zengmei123@gmail.com. AD - Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, 234# Fujiang Road, Nanchong, 637001, Sichuan Province, China. zengmei123@gmail.com. AD - Medical Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan, China. zengmei123@gmail.com. AD - The Fifth People's Hospital of Nanchong City, 21# Bajiao Street, Nanchong, 637100, Sichuan, China. zengmei123@gmail.com. LA - eng GR - 81972119/National Natural Science Foundation of China/ GR - 22NSFSC0781/Sichuan Province Science and Technology Support Program/ PT - Journal Article DEP - 20231123 PL - England TA - Mol Med JT - Molecular medicine (Cambridge, Mass.) JID - 9501023 RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 268B43MJ25 (Uric Acid) RN - 0 (NF-E2-Related Factor 2) SB - IM MH - Mice MH - Animals MH - Kelch-Like ECH-Associated Protein 1/metabolism MH - *Uric Acid MH - NF-E2-Related Factor 2/metabolism MH - Inflammation/metabolism MH - *Peritonitis PMC - PMC10668345 OTO - NOTNLM OT - FAO OT - Keap1-Nrf2 signaling axis OT - MSUc OT - MaR1 OT - Prdx5 COIS- The authors declare no conflict of interest. EDAT- 2023/11/24 00:42 MHDA- 2023/11/27 12:44 PMCR- 2023/11/23 CRDT- 2023/11/23 23:51 PHST- 2023/06/20 00:00 [received] PHST- 2023/11/10 00:00 [accepted] PHST- 2023/11/27 12:44 [medline] PHST- 2023/11/24 00:42 [pubmed] PHST- 2023/11/23 23:51 [entrez] PHST- 2023/11/23 00:00 [pmc-release] AID - 10.1186/s10020-023-00756-w [pii] AID - 756 [pii] AID - 10.1186/s10020-023-00756-w [doi] PST - epublish SO - Mol Med. 2023 Nov 23;29(1):158. doi: 10.1186/s10020-023-00756-w.