PMID- 31367941 OWN - NLM STAT- MEDLINE DCOM- 20200330 LR - 20200624 IS - 1434-9949 (Electronic) IS - 0770-3198 (Linking) VI - 38 IP - 11 DP - 2019 Nov TI - Sirt1 inhibits gouty arthritis via activating PPARgamma. PG - 3235-3242 LID - 10.1007/s10067-019-04697-w [doi] AB - OBJECTIVE: To identify the effects of Sirtuin 1 (Sirt1) on gouty arthritis and investigate the underlying mechanisms. METHODS: A gouty arthritis model was established by intra-articular injection of monosodium urate (MSU, 1 mg) crystal solution into the left foot pad of C57BL/6 mice. After pretreating the gouty arthritis mice with intra-articular injection of Sirt1 agonist (Resveratrol, RSV, 20 mg/kg) or peroxisome proliferator-activated receptor gamma (PPARgamma) inhibitor (T0070907, 1 mg/kg), the degree of joint inflammation of the gouty arthritis mice was evaluated by clinical integration of joint inflammation and hematoxylin and eosin (H&E) staining. The mRNA expression of Sirt1 and PPARgamma were determined by real-time polymerase chain reaction (PCR). The expression profiling of inflammatory cytokines and chemokines in mouse joint tissues were determined by multi-factor assay kits. Peritoneal macrophages were isolated from mice and tested the effects of RSV and/or PPARgamma on pro-inflammatory cytokines secretion by PCR. RESULTS: Sirt1 agonist significantly suppressed the onset of gouty arthritis induced by MSU and reduced the infiltration of inflammatory cells in the joints. Sirt1 agonist significantly promoted the expression of PPARgamma, while decreased the expression of interleukin (IL)-1beta, IL-1alpha, IL-6, interferon-gamma (IFN-gamma), monocyte chemotactic protein 1(MCP-1), tumor necrosis factor a (TNF-alpha), and chemokines (CXCL-1, CXCL-5, CCL-22) induced by MSU in joint tissues. After blocking PPARgamma with T0070907 or by siRNA, the anti-inflammatory effect of Sirt1 agonist on gouty arthritis disappeared and the expression of pro-inflammatory molecules were not significantly reduced. CONCLUSIONS: Sirt1 may control the acute onset of gouty arthritis in mice by inhibiting the infiltration of inflammatory cells and the secretion of pro-inflammatory molecules through PPARgamma. Key Points * Sirt1 and its activator, RSV, attenuate the severity of gouty arthritis in mice. * Sirt1 inhibits the infiltration of inflammatory cells and the secretion of pro-inflammatory molecules in MSU-induced arthritis. * Sirt1 inhibits inflammation partially dependent on PPARgamma. FAU - Wang, Juan AU - Wang J AD - Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. FAU - Chen, Guangliang AU - Chen G AD - Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. AD - Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Rd, Shanghai, 200032, China. FAU - Lu, Liangjing AU - Lu L AD - Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. lu_liangjing@163.com. FAU - Zou, Hejian AU - Zou H AD - Division of Rheumatology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. hjzou@fudan.edu.cn. AD - Institute of Rheumatology, Immunology and Allergy, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12, Middle Wulumuqi Road, Shanghai, 200040, China. hjzou@fudan.edu.cn. LA - eng GR - 2017YFC0909002/the National Key Research and Development Program of China/ GR - No. 81671588/the National Natural Science Foundation of China/ GR - No. 81801593/the National Natural Science Foundation of China/ GR - No. 81802362/the National Natural Science Foundation of China/ GR - No. square square16CR3012A/the Research Funding from Shanghai Hospital Development Center/ PT - Journal Article DEP - 20190731 PL - Germany TA - Clin Rheumatol JT - Clinical rheumatology JID - 8211469 RN - 0 (Cytokines) RN - 0 (PPAR gamma) RN - EC 3.5.1.- (Sirt1 protein, mouse) RN - EC 3.5.1.- (Sirtuin 1) RN - Q369O8926L (Resveratrol) SB - IM MH - Animals MH - Arthritis, Gouty/etiology/*metabolism MH - Cytokines/metabolism MH - Mice, Inbred C57BL MH - PPAR gamma/antagonists & inhibitors/*metabolism MH - Resveratrol MH - Sirtuin 1/*metabolism OTO - NOTNLM OT - Gouty arthritis OT - PPARgamma OT - Sirt1 EDAT- 2019/08/02 06:00 MHDA- 2020/03/31 06:00 CRDT- 2019/08/02 06:00 PHST- 2019/03/28 00:00 [received] PHST- 2019/07/15 00:00 [accepted] PHST- 2019/06/25 00:00 [revised] PHST- 2019/08/02 06:00 [pubmed] PHST- 2020/03/31 06:00 [medline] PHST- 2019/08/02 06:00 [entrez] AID - 10.1007/s10067-019-04697-w [pii] AID - 10.1007/s10067-019-04697-w [doi] PST - ppublish SO - Clin Rheumatol. 2019 Nov;38(11):3235-3242. doi: 10.1007/s10067-019-04697-w. Epub 2019 Jul 31.