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HSP60 is a highly conserved stress protein that acts as a cellular \u201cdanger\u201d signal for immune reactions. In this study, we aimed to investigate the role and molecular mechanism of HSP60 in gout. HSP60 expression was detected in peripheral blood mononuclear cells (PBMCs) and plasma of gout patients. The effect and molecular mechanism of HSP60 in gout were studied in MSU crystals treatment macrophages and C57BL\/6 mice. JC-1 probe and MitoSOX Red were used to measure the mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS). HSP60 expression was significantly upregulated in the PBMCs and sera of patients with acute gout (AG) compared to those with intercritical gout (IG) or healthy controls (HCs). MSU crystals induced the expression and secretion of HSP60 in the macrophages. HSP60 knockdown or overexpression affects TLR4 and MyD88 expression, I\u03baB\u03b1 degradation, and the nuclear localization of NF-\u03baB in MSU crystal-stimulated inflammation. Further, HSP60 facilitates MMP collapse and mtROS production and activates the NLRP3 inflammasome in MSU crystal-stimulated macrophages. In MSU crystal-induced arthritis mouse models pretreated with HSP60 vivo-morpholino, paw swelling, myeloperoxidase (MPO) activity, and inflammatory cell infiltration significantly decreased. Our study reveals that MSU crystal stimulates the expression of HSP60, which accelerates the TLR4-MyD88-NF-\u03baB signaling pathway and exacerbates mitochondrial dysfunction.<\/jats:p>","DOI":"10.1155\/2020\/8706898","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T17:50:09Z","timestamp":1609437009000},"page":"1-16","source":"Crossref","is-referenced-by-count":51,"title":["HSP60 Regulates Monosodium Urate Crystal-Induced Inflammation by Activating the TLR4-NF-\u03baB-MyD88 Signaling Pathway and Disrupting Mitochondrial Function"],"prefix":"10.1155","volume":"2020","author":[{"given":"Qiushi","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Nanchong, 637000 Sichuan, Nanchong, China"},{"name":"Preclinical School of North Sichuan Medical College, 234# Fujiang Road, Nanchong, 637000 Sichuan, Nanchong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Nanchong, 637000 Sichuan, Nanchong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Mu","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Nanchong, 637000 Sichuan, Nanchong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Qin","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Nanchong, 637000 Sichuan, Nanchong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Long","sequence":"additional","affiliation":[{"name":"The Fifth People\u2019s Hospital of Nanchong City, 21#Bajiao Street, Nanchong 637100, Sichuan, Nanchong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Ren","sequence":"additional","affiliation":[{"name":"The Fifth People\u2019s Hospital of Nanchong City, 21#Bajiao Street, Nanchong 637100, Sichuan, Nanchong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Nanchong, 637000 Sichuan, Nanchong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Nanchong, 637000 Sichuan, Nanchong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5661-7101","authenticated-orcid":true,"given":"Mei","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Nanchong, 637000 Sichuan, Nanchong, China"},{"name":"Preclinical School of North Sichuan Medical College, 234# Fujiang Road, Nanchong, 637000 Sichuan, Nanchong, China"},{"name":"The Fifth People\u2019s Hospital of Nanchong City, 21#Bajiao Street, Nanchong 637100, Sichuan, Nanchong, China"},{"name":"Medical Imaging Key Laboratory of Sichuan Province, North Sichuan Medical College, 234# Fujiang Road, Nanchong 637000, Sichuan, Nanchong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40807"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01991"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-015-2991-1"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209707"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez384"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.1.189"},{"issue":"1","key":"7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1379\/1466-1268(1999)004<0029:IOHHSP>2.3.CO;2","article-title":"Identifification of human heat shock protein 60 (Hsp 60) and anti-Hsp 60 antibodies in the peripheral circulation of normal individuals","volume":"4","author":"A. 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