Sirt1 inhibits gouty arthritis via activating PPARγ

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...

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Veröffentlicht in:Clinical rheumatology 2019-11, Vol.38 (11), p.3235-3242
Hauptverfasser: Wang, Juan, Chen, Guangliang, Lu, Liangjing, Zou, Hejian
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container_title Clinical rheumatology
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creator Wang, Juan
Chen, Guangliang
Lu, Liangjing
Zou, Hejian
description 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 γ (PPARγ) 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 PPARγ 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 PPARγ 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 PPARγ, while decreased the expression of interleukin (IL)-1β, IL-1α, IL-6, interferon-γ (IFN-γ), monocyte chemotactic protein 1(MCP-1), tumor necrosis factor a (TNF-α), and chemokines (CXCL-1, CXCL-5, CCL-22) induced by MSU in joint tissues. After blocking PPARγ 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 PPARγ. 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 PPARγ.
doi_str_mv 10.1007/s10067-019-04697-w
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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 γ (PPARγ) 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&amp;E) staining. The mRNA expression of Sirt1 and PPARγ 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 PPARγ 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 PPARγ, while decreased the expression of interleukin (IL)-1β, IL-1α, IL-6, interferon-γ (IFN-γ), monocyte chemotactic protein 1(MCP-1), tumor necrosis factor a (TNF-α), and chemokines (CXCL-1, CXCL-5, CCL-22) induced by MSU in joint tissues. After blocking PPARγ 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 PPARγ. 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 PPARγ.</description><identifier>ISSN: 0770-3198</identifier><identifier>EISSN: 1434-9949</identifier><identifier>DOI: 10.1007/s10067-019-04697-w</identifier><identifier>PMID: 31367941</identifier><language>eng</language><publisher>London: Springer London</publisher><subject>Agonists ; Animals ; Arthritis ; Arthritis, Gouty - etiology ; Arthritis, Gouty - metabolism ; Chemokines ; Cytokines ; Cytokines - metabolism ; Gene expression ; Inflammation ; Injection ; Interleukin 6 ; Joint diseases ; Macrophages ; Medicine ; Medicine &amp; Public Health ; Metastases ; Mice, Inbred C57BL ; Monocyte chemoattractant protein 1 ; Monocytes ; Original Article ; Peritoneum ; Polymerase chain reaction ; PPAR gamma - antagonists &amp; inhibitors ; PPAR gamma - metabolism ; Resveratrol ; Rheumatology ; siRNA ; SIRT1 protein ; Sirtuin 1 - metabolism ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Uric acid ; γ-Interferon</subject><ispartof>Clinical rheumatology, 2019-11, Vol.38 (11), p.3235-3242</ispartof><rights>International League of Associations for Rheumatology (ILAR) 2019</rights><rights>Clinical Rheumatology is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-39db5ac21f1061841c1696a1d0c9e2cd3cd8fdcec763b44ef9092bfdcba64b7b3</citedby><cites>FETCH-LOGICAL-c375t-39db5ac21f1061841c1696a1d0c9e2cd3cd8fdcec763b44ef9092bfdcba64b7b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10067-019-04697-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10067-019-04697-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31367941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Juan</creatorcontrib><creatorcontrib>Chen, Guangliang</creatorcontrib><creatorcontrib>Lu, Liangjing</creatorcontrib><creatorcontrib>Zou, Hejian</creatorcontrib><title>Sirt1 inhibits gouty arthritis via activating PPARγ</title><title>Clinical rheumatology</title><addtitle>Clin Rheumatol</addtitle><addtitle>Clin Rheumatol</addtitle><description>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 γ (PPARγ) 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&amp;E) staining. The mRNA expression of Sirt1 and PPARγ 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 PPARγ 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 PPARγ, while decreased the expression of interleukin (IL)-1β, IL-1α, IL-6, interferon-γ (IFN-γ), monocyte chemotactic protein 1(MCP-1), tumor necrosis factor a (TNF-α), and chemokines (CXCL-1, CXCL-5, CCL-22) induced by MSU in joint tissues. After blocking PPARγ 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 PPARγ. 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 PPARγ.</description><subject>Agonists</subject><subject>Animals</subject><subject>Arthritis</subject><subject>Arthritis, Gouty - etiology</subject><subject>Arthritis, Gouty - metabolism</subject><subject>Chemokines</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Gene expression</subject><subject>Inflammation</subject><subject>Injection</subject><subject>Interleukin 6</subject><subject>Joint diseases</subject><subject>Macrophages</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Metastases</subject><subject>Mice, Inbred C57BL</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Monocytes</subject><subject>Original Article</subject><subject>Peritoneum</subject><subject>Polymerase chain reaction</subject><subject>PPAR gamma - antagonists &amp; inhibitors</subject><subject>PPAR gamma - metabolism</subject><subject>Resveratrol</subject><subject>Rheumatology</subject><subject>siRNA</subject><subject>SIRT1 protein</subject><subject>Sirtuin 1 - metabolism</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Uric acid</subject><subject>γ-Interferon</subject><issn>0770-3198</issn><issn>1434-9949</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kMtKAzEUhoMotlZfwIUMuHEzmpOkSbMsxRsULF7WIZPJtCntTE0yLX0u38NncnpRwYWbBJLv_8_hQ-gc8DVgLG5Cc3KRYpApZlyKdHWA2sAoS6Vk8hC1sRA4pSB7LXQSwhRjTHoSjlGLAuVCMmgj9uJ8hMSVE5e5GJJxVcd1on2ceBddSJZOJ9pEt9TRleNkNOo_f36coqNCz4I9298d9HZ3-zp4SIdP94-D_jA1VHRjSmWedbUhUADm0GNggEuuIcdGWmJyavJekRtrBKcZY7aQWJKseck0Z5nIaAdd7XoXvnqvbYhq7oKxs5kubVUHRQgXggkioEEv_6DTqvZls92WIkIC3lBkRxlfheBtoRbezbVfK8Bq41TtnKrGqdo6VasmdLGvrrO5zX8i3xIbgO6A0HyVY-t_Z_9T-wXJkII5</recordid><startdate>20191101</startdate><enddate>20191101</enddate><creator>Wang, Juan</creator><creator>Chen, Guangliang</creator><creator>Lu, Liangjing</creator><creator>Zou, Hejian</creator><general>Springer London</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20191101</creationdate><title>Sirt1 inhibits gouty arthritis via activating PPARγ</title><author>Wang, Juan ; Chen, Guangliang ; Lu, Liangjing ; Zou, Hejian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-39db5ac21f1061841c1696a1d0c9e2cd3cd8fdcec763b44ef9092bfdcba64b7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Agonists</topic><topic>Animals</topic><topic>Arthritis</topic><topic>Arthritis, Gouty - etiology</topic><topic>Arthritis, Gouty - metabolism</topic><topic>Chemokines</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Gene expression</topic><topic>Inflammation</topic><topic>Injection</topic><topic>Interleukin 6</topic><topic>Joint diseases</topic><topic>Macrophages</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Metastases</topic><topic>Mice, Inbred C57BL</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Monocytes</topic><topic>Original Article</topic><topic>Peritoneum</topic><topic>Polymerase chain reaction</topic><topic>PPAR gamma - antagonists &amp; inhibitors</topic><topic>PPAR gamma - metabolism</topic><topic>Resveratrol</topic><topic>Rheumatology</topic><topic>siRNA</topic><topic>SIRT1 protein</topic><topic>Sirtuin 1 - metabolism</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><topic>Uric acid</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Juan</creatorcontrib><creatorcontrib>Chen, Guangliang</creatorcontrib><creatorcontrib>Lu, Liangjing</creatorcontrib><creatorcontrib>Zou, Hejian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical rheumatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Juan</au><au>Chen, Guangliang</au><au>Lu, Liangjing</au><au>Zou, Hejian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sirt1 inhibits gouty arthritis via activating PPARγ</atitle><jtitle>Clinical rheumatology</jtitle><stitle>Clin Rheumatol</stitle><addtitle>Clin Rheumatol</addtitle><date>2019-11-01</date><risdate>2019</risdate><volume>38</volume><issue>11</issue><spage>3235</spage><epage>3242</epage><pages>3235-3242</pages><issn>0770-3198</issn><eissn>1434-9949</eissn><abstract>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 γ (PPARγ) 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&amp;E) staining. The mRNA expression of Sirt1 and PPARγ 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 PPARγ 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 PPARγ, while decreased the expression of interleukin (IL)-1β, IL-1α, IL-6, interferon-γ (IFN-γ), monocyte chemotactic protein 1(MCP-1), tumor necrosis factor a (TNF-α), and chemokines (CXCL-1, CXCL-5, CCL-22) induced by MSU in joint tissues. After blocking PPARγ 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 PPARγ. 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 PPARγ.</abstract><cop>London</cop><pub>Springer London</pub><pmid>31367941</pmid><doi>10.1007/s10067-019-04697-w</doi><tpages>8</tpages></addata></record>
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subjects Agonists
Animals
Arthritis
Arthritis, Gouty - etiology
Arthritis, Gouty - metabolism
Chemokines
Cytokines
Cytokines - metabolism
Gene expression
Inflammation
Injection
Interleukin 6
Joint diseases
Macrophages
Medicine
Medicine & Public Health
Metastases
Mice, Inbred C57BL
Monocyte chemoattractant protein 1
Monocytes
Original Article
Peritoneum
Polymerase chain reaction
PPAR gamma - antagonists & inhibitors
PPAR gamma - metabolism
Resveratrol
Rheumatology
siRNA
SIRT1 protein
Sirtuin 1 - metabolism
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Uric acid
γ-Interferon
title Sirt1 inhibits gouty arthritis via activating PPARγ
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