PMID- 29996893 OWN - NLM STAT- MEDLINE DCOM- 20190514 LR - 20190514 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 20 IP - 1 DP - 2018 Jul 11 TI - miR-155 is dispensable in monosodium urate-induced gouty inflammation in mice. PG - 144 LID - 10.1186/s13075-018-1550-y [doi] LID - 144 AB - BACKGROUND: The findings of a previous study by Jin et al. have shown that microRNA (miR)-155 was upregulated in patients with acute gouty arthritis and enhanced the proinflammatory cytokines. There is no direct evidence to support that miR-155 is indeed involved in monosodium urate (MSU)-induced inflammatory responses in vivo. The aim of this study was to investigate the role of miR-155 knock-out (KO) or knock-in (KI) mice in MSU-induced animal models to mimic acute gout. METHODS: MiR-155 expression in cultured bone marrow-derived macrophages (BMDMs) from miR-155 KO, miR-155 KI, and wild-type (WT) mice treated with MSU crystals in vitro was detected by real-time quantitative polymerase chain reaction (qPCR). MiR-155 KO and WT mice were used to induce an acute gouty inflammatory response with MSU crystals including models of foot pad inflammation, ankle arthritis, air pouch inflammation, and peritonitis. Furthermore, the proinflammatory interleukin (IL)-1beta levels in lavage fluids from air pouch and peritoneal cavity models were measured by enzyme-linked immunosorbent assay (ELISA), and tumor necrosis factor (TNF)-alpha production from BMDMs of miR-155 KI mice treated with MSU were measured by flow cytometry. RESULTS: MiR-155 expression was quickly upregulated in BMDMs from WT mice following MSU treatment in vitro. In comparison with WT mice in vivo, the swelling index of miR-155 KO mice showed no significant difference in the murine foot pad and ankle arthritis models for the indicated different time points. There were similar changes in total cell numbers of lavage fluids in the air pouch and peritoneal cavity models between miR-155 KO and WT mice following MSU crystal injection. Moreover, the IL-1beta levels of lavage fluids in the air pouch and peritonitis models from miR-155 KO mice were almost the same as those from WT mice. TNF-alpha levels were comparable from BMDMs treated with MSU crystals in vitro between miR-155 KI mice and WT mice. CONCLUSIONS: MiR-155 is dispensable in MSU-induced gouty inflammation in mice. Deletion of miR-155 might not be an effective therapeutic approach to relieve the inflammation in acute gout. FAU - Yang, Qibin AU - Yang Q AD - Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Sichuan Province, Nanchong, 637000, China. AD - Henry Ford Immunology Program, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. AD - Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. FAU - Zhang, Quanbo AU - Zhang Q AD - Department of Gerontology, Affiliated Hospital of North Sichuan Medical College, Sichuan Province, Nanchong, 637000, China. AD - Henry Ford Immunology Program, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. AD - Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. FAU - Qing, Yufeng AU - Qing Y AD - Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Sichuan Province, Nanchong, 637000, China. FAU - Zhou, Li AU - Zhou L AD - Henry Ford Immunology Program, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. AD - Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. AD - Department of Internal Medicine, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. FAU - Mi, Qingsheng AU - Mi Q AD - Henry Ford Immunology Program, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. qmil@hfhs.org. AD - Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. qmil@hfhs.org. AD - Department of Internal Medicine, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA. qmil@hfhs.org. FAU - Zhou, Jingguo AU - Zhou J AD - Department of Rheumatology and Immunology, The First Affiliated Hospital of Chengdu Medical College, Sichuan Province, Chengdu, 610000, China. jgzhou@cmc.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180711 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (MicroRNAs) RN - 0 (Mirn155 microRNA, mouse) RN - 268B43MJ25 (Uric Acid) SB - IM EIN - Arthritis Res Ther. 2018 Aug 14;20(1):177. PMID: 30107821 MH - Animals MH - Arthritis, Experimental/chemically induced/*genetics MH - Arthritis, Gouty/*genetics MH - Gene Knock-In Techniques MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - MicroRNAs/*genetics MH - Uric Acid/toxicity PMC - PMC6042462 OTO - NOTNLM OT - Gout OT - Inflammation OT - MSU OT - MiR-155 COIS- ETHICS APPROVAL: All animal experimental procedures in the current study were approved by the Institutional Animal Care and Use Committee of Henry Ford Health System (Detroit, USA). CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/07/13 06:00 MHDA- 2019/05/15 06:00 PMCR- 2018/07/11 CRDT- 2018/07/13 06:00 PHST- 2017/10/31 00:00 [received] PHST- 2018/02/21 00:00 [accepted] PHST- 2018/07/13 06:00 [entrez] PHST- 2018/07/13 06:00 [pubmed] PHST- 2019/05/15 06:00 [medline] PHST- 2018/07/11 00:00 [pmc-release] AID - 10.1186/s13075-018-1550-y [pii] AID - 1550 [pii] AID - 10.1186/s13075-018-1550-y [doi] PST - epublish SO - Arthritis Res Ther. 2018 Jul 11;20(1):144. doi: 10.1186/s13075-018-1550-y.