Adenovirus-Mediated Small Interfering RNA Targeting TAK1 Ameliorates Joint Inflammation with Collagen-Induced Arthritis in Mice
Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammato...
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| Veröffentlicht in: | Inflammation 2017-06, Vol.40 (3), p.894-903 |
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| creator | Luo, Xinjing Chen, Yongfeng Lv, Guoju Zhou, Zhidong Chen, Jie Mo, Xuanrong Xie, Jiangwen |
| description | Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice. Ad-siRNA-TAK1 was constructed. The murine RAW 264.7 macrophages were infected with ad-siRNA-TAK1, and the silencing specificity of TAK1 was assessed by quantitative polymerase chain reaction (PCR) and western blot. DBA/1 mice were injected intra-articularly with ad-siRNA-TAK1. Development and severity of arthritis was assessed histologically. Synovial inflammation and bone destruction were determined by hematoxylin and eosin (HE) staining. Articular and serum concentrations of tumor necrosis factor-α, interleukin-1, and interleukin-6 were determined using enzyme-linked immunosorbent assay. Levels of phosphorylated p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) were detected by western blot.
In vitro
, ad--siRNA-TAK1 efficiently inhibited the expression of TAK1 at both mRNA and protein levels.
In vivo
, intra-articular injection of ad-siRNA-TAK1 efficiently alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed JNK pathways. Our results demonstrate the efficiency of ad--siRNA-TAK1 in controlling joint inflammation of CIA, which is associated with the suppression of the expression of pro-inflammatory cytokines and JNK activation. |
| doi_str_mv | 10.1007/s10753-017-0534-4 |
| format | Article |
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In vitro
, ad--siRNA-TAK1 efficiently inhibited the expression of TAK1 at both mRNA and protein levels.
In vivo
, intra-articular injection of ad-siRNA-TAK1 efficiently alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed JNK pathways. Our results demonstrate the efficiency of ad--siRNA-TAK1 in controlling joint inflammation of CIA, which is associated with the suppression of the expression of pro-inflammatory cytokines and JNK activation.</description><identifier>ISSN: 0360-3997</identifier><identifier>EISSN: 1573-2576</identifier><identifier>DOI: 10.1007/s10753-017-0534-4</identifier><identifier>PMID: 28220341</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adenoviridae - genetics ; Animals ; Arthritis ; Arthritis, Rheumatoid - chemically induced ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - prevention & control ; Biomedical and Life Sciences ; Biomedicine ; c-Jun protein ; Collagen ; Cytokines ; Cytokines - drug effects ; Enzyme-linked immunosorbent assay ; Extracellular signal-regulated kinase ; Gene Silencing ; Immunology ; Inflammation ; Inflammation - drug therapy ; Inflammation - prevention & control ; Inflammatory diseases ; Injections, Intra-Articular ; Interleukin 1 ; Interleukin 6 ; Internal Medicine ; JNK Mitogen-Activated Protein Kinases - drug effects ; JNK protein ; Joints - pathology ; Kinases ; Macrophages ; MAP Kinase Kinase Kinases - antagonists & inhibitors ; MAP Kinase Kinase Kinases - genetics ; Mice ; mRNA ; Original Article ; Pathology ; Pharmacology/Toxicology ; Polymerase chain reaction ; RAW 264.7 Cells ; Rheumatoid arthritis ; Rheumatology ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - pharmacology ; siRNA ; TAK1 protein ; Transcription factors</subject><ispartof>Inflammation, 2017-06, Vol.40 (3), p.894-903</ispartof><rights>Springer Science+Business Media New York 2017</rights><rights>Inflammation is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-b61dc206793393ff95465e7e978c5f25a865246d0f591300602cea1620c11fab3</citedby><cites>FETCH-LOGICAL-c372t-b61dc206793393ff95465e7e978c5f25a865246d0f591300602cea1620c11fab3</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/s10753-017-0534-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10753-017-0534-4$$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/28220341$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Xinjing</creatorcontrib><creatorcontrib>Chen, Yongfeng</creatorcontrib><creatorcontrib>Lv, Guoju</creatorcontrib><creatorcontrib>Zhou, Zhidong</creatorcontrib><creatorcontrib>Chen, Jie</creatorcontrib><creatorcontrib>Mo, Xuanrong</creatorcontrib><creatorcontrib>Xie, Jiangwen</creatorcontrib><title>Adenovirus-Mediated Small Interfering RNA Targeting TAK1 Ameliorates Joint Inflammation with Collagen-Induced Arthritis in Mice</title><title>Inflammation</title><addtitle>Inflammation</addtitle><addtitle>Inflammation</addtitle><description>Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice. Ad-siRNA-TAK1 was constructed. The murine RAW 264.7 macrophages were infected with ad-siRNA-TAK1, and the silencing specificity of TAK1 was assessed by quantitative polymerase chain reaction (PCR) and western blot. DBA/1 mice were injected intra-articularly with ad-siRNA-TAK1. Development and severity of arthritis was assessed histologically. Synovial inflammation and bone destruction were determined by hematoxylin and eosin (HE) staining. Articular and serum concentrations of tumor necrosis factor-α, interleukin-1, and interleukin-6 were determined using enzyme-linked immunosorbent assay. Levels of phosphorylated p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) were detected by western blot.
In vitro
, ad--siRNA-TAK1 efficiently inhibited the expression of TAK1 at both mRNA and protein levels.
In vivo
, intra-articular injection of ad-siRNA-TAK1 efficiently alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed JNK pathways. Our results demonstrate the efficiency of ad--siRNA-TAK1 in controlling joint inflammation of CIA, which is associated with the suppression of the expression of pro-inflammatory cytokines and JNK activation.</description><subject>Adenoviridae - genetics</subject><subject>Animals</subject><subject>Arthritis</subject><subject>Arthritis, Rheumatoid - chemically induced</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Arthritis, Rheumatoid - prevention & control</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>c-Jun protein</subject><subject>Collagen</subject><subject>Cytokines</subject><subject>Cytokines - drug effects</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Extracellular signal-regulated kinase</subject><subject>Gene Silencing</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - prevention & control</subject><subject>Inflammatory diseases</subject><subject>Injections, Intra-Articular</subject><subject>Interleukin 1</subject><subject>Interleukin 6</subject><subject>Internal Medicine</subject><subject>JNK Mitogen-Activated Protein Kinases - drug effects</subject><subject>JNK protein</subject><subject>Joints - pathology</subject><subject>Kinases</subject><subject>Macrophages</subject><subject>MAP Kinase Kinase Kinases - antagonists & inhibitors</subject><subject>MAP Kinase Kinase Kinases - genetics</subject><subject>Mice</subject><subject>mRNA</subject><subject>Original Article</subject><subject>Pathology</subject><subject>Pharmacology/Toxicology</subject><subject>Polymerase chain reaction</subject><subject>RAW 264.7 Cells</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatology</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>siRNA</subject><subject>TAK1 protein</subject><subject>Transcription factors</subject><issn>0360-3997</issn><issn>1573-2576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcGKFDEQhoMo7rj6AF4k4MVLtJJ0ku5jM6zu6K6Cjucm0109m6U7GZO04mlf3QyzigieQsH3_ynqI-Q5h9ccwLxJHIySDLhhoGTFqgdkxZWRTCijH5IVSA1MNo05I09SugWAuqnlY3ImaiFAVnxF7toBffju4pLYNQ7OZhzol9lOE934jHHE6Pyefv7Y0q2Ne8zHadt-4LSdcXIhlkCi74PzuQTGyc6zzS54-sPlG7oO02T36NnGD0tfmtuYb6LLLlHn6bXr8Sl5NNop4bP795x8fXuxXV-yq0_vNuv2ivXSiMx2mg-9AG0aKRs5jo2qtEKDjal7NQpla61EpQcYVcMlgAbRo-VaQM_5aHfynLw69R5i-LZgyt3sUo9lPY9hSR2vDehKgxIFffkPehuW6Mt2hSrHhFoALxQ_UX0MKUUcu0N0s40_Ow7d0U53stMVO93RTleVzIv75mU34_An8VtHAcQJSIfj2TH-9fV_W38B6xyZEA</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Luo, Xinjing</creator><creator>Chen, Yongfeng</creator><creator>Lv, Guoju</creator><creator>Zhou, Zhidong</creator><creator>Chen, Jie</creator><creator>Mo, Xuanrong</creator><creator>Xie, Jiangwen</creator><general>Springer US</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>7TO</scope><scope>7U9</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>20170601</creationdate><title>Adenovirus-Mediated Small Interfering RNA Targeting TAK1 Ameliorates Joint Inflammation with Collagen-Induced Arthritis in Mice</title><author>Luo, Xinjing ; Chen, Yongfeng ; Lv, Guoju ; Zhou, Zhidong ; Chen, Jie ; Mo, Xuanrong ; Xie, Jiangwen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-b61dc206793393ff95465e7e978c5f25a865246d0f591300602cea1620c11fab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adenoviridae - genetics</topic><topic>Animals</topic><topic>Arthritis</topic><topic>Arthritis, Rheumatoid - chemically induced</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Arthritis, Rheumatoid - prevention & control</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>c-Jun protein</topic><topic>Collagen</topic><topic>Cytokines</topic><topic>Cytokines - drug effects</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Extracellular signal-regulated kinase</topic><topic>Gene Silencing</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - prevention & control</topic><topic>Inflammatory diseases</topic><topic>Injections, Intra-Articular</topic><topic>Interleukin 1</topic><topic>Interleukin 6</topic><topic>Internal Medicine</topic><topic>JNK Mitogen-Activated Protein Kinases - drug effects</topic><topic>JNK protein</topic><topic>Joints - pathology</topic><topic>Kinases</topic><topic>Macrophages</topic><topic>MAP Kinase Kinase Kinases - antagonists & inhibitors</topic><topic>MAP Kinase Kinase Kinases - genetics</topic><topic>Mice</topic><topic>mRNA</topic><topic>Original Article</topic><topic>Pathology</topic><topic>Pharmacology/Toxicology</topic><topic>Polymerase chain reaction</topic><topic>RAW 264.7 Cells</topic><topic>Rheumatoid arthritis</topic><topic>Rheumatology</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>siRNA</topic><topic>TAK1 protein</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Xinjing</creatorcontrib><creatorcontrib>Chen, Yongfeng</creatorcontrib><creatorcontrib>Lv, Guoju</creatorcontrib><creatorcontrib>Zhou, Zhidong</creatorcontrib><creatorcontrib>Chen, Jie</creatorcontrib><creatorcontrib>Mo, Xuanrong</creatorcontrib><creatorcontrib>Xie, Jiangwen</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>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & 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 & Medical Complete (Alumni)</collection><collection>Health & 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>Inflammation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Xinjing</au><au>Chen, Yongfeng</au><au>Lv, Guoju</au><au>Zhou, Zhidong</au><au>Chen, Jie</au><au>Mo, Xuanrong</au><au>Xie, Jiangwen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenovirus-Mediated Small Interfering RNA Targeting TAK1 Ameliorates Joint Inflammation with Collagen-Induced Arthritis in Mice</atitle><jtitle>Inflammation</jtitle><stitle>Inflammation</stitle><addtitle>Inflammation</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>40</volume><issue>3</issue><spage>894</spage><epage>903</epage><pages>894-903</pages><issn>0360-3997</issn><eissn>1573-2576</eissn><abstract>Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice. Ad-siRNA-TAK1 was constructed. The murine RAW 264.7 macrophages were infected with ad-siRNA-TAK1, and the silencing specificity of TAK1 was assessed by quantitative polymerase chain reaction (PCR) and western blot. DBA/1 mice were injected intra-articularly with ad-siRNA-TAK1. Development and severity of arthritis was assessed histologically. Synovial inflammation and bone destruction were determined by hematoxylin and eosin (HE) staining. Articular and serum concentrations of tumor necrosis factor-α, interleukin-1, and interleukin-6 were determined using enzyme-linked immunosorbent assay. Levels of phosphorylated p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) were detected by western blot.
In vitro
, ad--siRNA-TAK1 efficiently inhibited the expression of TAK1 at both mRNA and protein levels.
In vivo
, intra-articular injection of ad-siRNA-TAK1 efficiently alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed JNK pathways. Our results demonstrate the efficiency of ad--siRNA-TAK1 in controlling joint inflammation of CIA, which is associated with the suppression of the expression of pro-inflammatory cytokines and JNK activation.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28220341</pmid><doi>10.1007/s10753-017-0534-4</doi><tpages>10</tpages></addata></record> |
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| ispartof | Inflammation, 2017-06, Vol.40 (3), p.894-903 |
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| subjects | Adenoviridae - genetics Animals Arthritis Arthritis, Rheumatoid - chemically induced Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - prevention & control Biomedical and Life Sciences Biomedicine c-Jun protein Collagen Cytokines Cytokines - drug effects Enzyme-linked immunosorbent assay Extracellular signal-regulated kinase Gene Silencing Immunology Inflammation Inflammation - drug therapy Inflammation - prevention & control Inflammatory diseases Injections, Intra-Articular Interleukin 1 Interleukin 6 Internal Medicine JNK Mitogen-Activated Protein Kinases - drug effects JNK protein Joints - pathology Kinases Macrophages MAP Kinase Kinase Kinases - antagonists & inhibitors MAP Kinase Kinase Kinases - genetics Mice mRNA Original Article Pathology Pharmacology/Toxicology Polymerase chain reaction RAW 264.7 Cells Rheumatoid arthritis Rheumatology RNA, Small Interfering - administration & dosage RNA, Small Interfering - pharmacology siRNA TAK1 protein Transcription factors |
| title | Adenovirus-Mediated Small Interfering RNA Targeting TAK1 Ameliorates Joint Inflammation with Collagen-Induced Arthritis in Mice |
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