TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis
Abstract Objectives Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear. The aim of this study was t...
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| Veröffentlicht in: | Rheumatology (Oxford, England) England), 2024-05, Vol.63 (6), p.1710-1719 |
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| creator | Kong, Xiangzhen Jiang, Shuai He, Qiuyu Shi, Xiangguang Pu, Weilin Huang, Yan Ma, Yanyun Liu, Qingmei Sun, Dayan Huang, Delin Wu, Fei Li, Pengcheng Tu, Wenzhen Zhao, Yinhuan Wang, Lei Chen, Yuanyuan Wu, Wenyu Tang, Yulong Zhao, Xiansheng Zhu, Qing Gao, Jian Xu, Weihong Shui, Xiaochuan Qian, Feng Wang, Jiucun |
| description | Abstract
Objectives
Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear. The aim of this study was to explore the roles and underlying mechanisms of TLR8 in SSc.
Methods
The expression of TLR8 was analysed, based on a public dataset, and then verified in skin tissues and skin fibroblasts of SSc patients. The role of TLR8 in inflammation and fibrosis was investigated using a TLR8-overexpression vector, activator (VTX-2337), inhibitor (cu-cpt-8m), and TLR8 siRNA in skin fibroblasts. The pathogenic role of TLR8 in skin inflammation and fibrosis was further validated in a bleomycin (BLM)-induced mouse skin inflammation and fibrosis model.
Results
TLR8 levels were significantly elevated in SSc skin tissues and myofibroblasts, along with significant activation of the TLR8 pathway. In vitro studies showed that overexpression or activation of TLR8 by a recombinant plasmid or VTX-2337 upregulated IL-6, IL-1β, COL I, COL III and α-SMA in skin fibroblasts. Consistently, both TLR8-siRNA and cu-cpt-8m reversed the phenotypes observed in TLR8-activating fibroblasts. Mechanistically, TLR8 induces skin fibrosis and inflammation in a manner dependent on the MAPK, NF-κB and SMAD2/3 pathways. Subcutaneous injection of cu-cpt-8m significantly alleviated BLM-induced skin inflammation and fibrosis in vivo.
Conclusion
TLR8 might be a promising therapeutic target for improving the treatment strategy for skin inflammation and fibrosis in SSc. |
| doi_str_mv | 10.1093/rheumatology/kead456 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2861305392</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/rheumatology/kead456</oup_id><sourcerecordid>3113482882</sourcerecordid><originalsourceid>FETCH-LOGICAL-c254t-a1fbcca7529f6ac96b3f907454236ce2a19a4e2678d146b7bb28737e0d1244fa3</originalsourceid><addsrcrecordid>eNqNkVtLw0AQhRdRbK3-A5EFX3yJ3Vt2k0cp3qAgSH0Os5tN3DaXmk2E_nu3F0V88mkG5juHmTkIXVJyS0nKp927HWro26otN9OVhVzE8giNqZAsIpyz45-eiRE6835JCIkpT07RiCspYyXUGJnF_DXBUJYdfEJvPfYr12DXFBXUwd21DYYmx4XTXeudx3qDwfQusK4p9_BupivwvQ9C7De-t7Uz2JvK7kTn6KSAytuLQ52gt4f7xewpmr88Ps_u5pFhsegjoIU2BlTM0kKCSaXmRUqUiAXj0lgGNAVhmVRJHg7TSmuWKK4sySkTogA-QTd733XXfgzW91ntvLFVBY1tB5-xRFJOYp6ygF7_QZft0DVhu4xTykXCkmRLiT1lwh2-s0W27lwN3SajJNuGkP0OITuEEGRXB_NB1zb_EX1_PQDTPdAO6_9ZfgFE-Zm7</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3113482882</pqid></control><display><type>article</type><title>TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><creator>Kong, Xiangzhen ; Jiang, Shuai ; He, Qiuyu ; Shi, Xiangguang ; Pu, Weilin ; Huang, Yan ; Ma, Yanyun ; Liu, Qingmei ; Sun, Dayan ; Huang, Delin ; Wu, Fei ; Li, Pengcheng ; Tu, Wenzhen ; Zhao, Yinhuan ; Wang, Lei ; Chen, Yuanyuan ; Wu, Wenyu ; Tang, Yulong ; Zhao, Xiansheng ; Zhu, Qing ; Gao, Jian ; Xu, Weihong ; Shui, Xiaochuan ; Qian, Feng ; Wang, Jiucun</creator><creatorcontrib>Kong, Xiangzhen ; Jiang, Shuai ; He, Qiuyu ; Shi, Xiangguang ; Pu, Weilin ; Huang, Yan ; Ma, Yanyun ; Liu, Qingmei ; Sun, Dayan ; Huang, Delin ; Wu, Fei ; Li, Pengcheng ; Tu, Wenzhen ; Zhao, Yinhuan ; Wang, Lei ; Chen, Yuanyuan ; Wu, Wenyu ; Tang, Yulong ; Zhao, Xiansheng ; Zhu, Qing ; Gao, Jian ; Xu, Weihong ; Shui, Xiaochuan ; Qian, Feng ; Wang, Jiucun</creatorcontrib><description>Abstract
Objectives
Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear. The aim of this study was to explore the roles and underlying mechanisms of TLR8 in SSc.
Methods
The expression of TLR8 was analysed, based on a public dataset, and then verified in skin tissues and skin fibroblasts of SSc patients. The role of TLR8 in inflammation and fibrosis was investigated using a TLR8-overexpression vector, activator (VTX-2337), inhibitor (cu-cpt-8m), and TLR8 siRNA in skin fibroblasts. The pathogenic role of TLR8 in skin inflammation and fibrosis was further validated in a bleomycin (BLM)-induced mouse skin inflammation and fibrosis model.
Results
TLR8 levels were significantly elevated in SSc skin tissues and myofibroblasts, along with significant activation of the TLR8 pathway. In vitro studies showed that overexpression or activation of TLR8 by a recombinant plasmid or VTX-2337 upregulated IL-6, IL-1β, COL I, COL III and α-SMA in skin fibroblasts. Consistently, both TLR8-siRNA and cu-cpt-8m reversed the phenotypes observed in TLR8-activating fibroblasts. Mechanistically, TLR8 induces skin fibrosis and inflammation in a manner dependent on the MAPK, NF-κB and SMAD2/3 pathways. Subcutaneous injection of cu-cpt-8m significantly alleviated BLM-induced skin inflammation and fibrosis in vivo.
Conclusion
TLR8 might be a promising therapeutic target for improving the treatment strategy for skin inflammation and fibrosis in SSc.</description><identifier>ISSN: 1462-0324</identifier><identifier>ISSN: 1462-0332</identifier><identifier>EISSN: 1462-0332</identifier><identifier>DOI: 10.1093/rheumatology/kead456</identifier><identifier>PMID: 37665747</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Autoimmunity ; Bleomycin ; Disease Models, Animal ; Female ; Fibroblasts ; Fibroblasts - metabolism ; Fibrosis ; Humans ; Inflammation ; Inflammation - metabolism ; Innate immunity ; Male ; MAP kinase ; Mice ; NF-κB protein ; Phenotypes ; Scleroderma, Systemic - immunology ; Scleroderma, Systemic - metabolism ; Scleroderma, Systemic - pathology ; Signal Transduction ; siRNA ; Skin ; Skin - immunology ; Skin - metabolism ; Skin - pathology ; Smad2 protein ; Systemic sclerosis ; Therapeutic targets ; Toll-Like Receptor 8 - metabolism</subject><ispartof>Rheumatology (Oxford, England), 2024-05, Vol.63 (6), p.1710-1719</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c254t-a1fbcca7529f6ac96b3f907454236ce2a19a4e2678d146b7bb28737e0d1244fa3</cites><orcidid>0000-0002-7794-2181</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,1585,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37665747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kong, Xiangzhen</creatorcontrib><creatorcontrib>Jiang, Shuai</creatorcontrib><creatorcontrib>He, Qiuyu</creatorcontrib><creatorcontrib>Shi, Xiangguang</creatorcontrib><creatorcontrib>Pu, Weilin</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>Ma, Yanyun</creatorcontrib><creatorcontrib>Liu, Qingmei</creatorcontrib><creatorcontrib>Sun, Dayan</creatorcontrib><creatorcontrib>Huang, Delin</creatorcontrib><creatorcontrib>Wu, Fei</creatorcontrib><creatorcontrib>Li, Pengcheng</creatorcontrib><creatorcontrib>Tu, Wenzhen</creatorcontrib><creatorcontrib>Zhao, Yinhuan</creatorcontrib><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Chen, Yuanyuan</creatorcontrib><creatorcontrib>Wu, Wenyu</creatorcontrib><creatorcontrib>Tang, Yulong</creatorcontrib><creatorcontrib>Zhao, Xiansheng</creatorcontrib><creatorcontrib>Zhu, Qing</creatorcontrib><creatorcontrib>Gao, Jian</creatorcontrib><creatorcontrib>Xu, Weihong</creatorcontrib><creatorcontrib>Shui, Xiaochuan</creatorcontrib><creatorcontrib>Qian, Feng</creatorcontrib><creatorcontrib>Wang, Jiucun</creatorcontrib><title>TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis</title><title>Rheumatology (Oxford, England)</title><addtitle>Rheumatology (Oxford)</addtitle><description>Abstract
Objectives
Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear. The aim of this study was to explore the roles and underlying mechanisms of TLR8 in SSc.
Methods
The expression of TLR8 was analysed, based on a public dataset, and then verified in skin tissues and skin fibroblasts of SSc patients. The role of TLR8 in inflammation and fibrosis was investigated using a TLR8-overexpression vector, activator (VTX-2337), inhibitor (cu-cpt-8m), and TLR8 siRNA in skin fibroblasts. The pathogenic role of TLR8 in skin inflammation and fibrosis was further validated in a bleomycin (BLM)-induced mouse skin inflammation and fibrosis model.
Results
TLR8 levels were significantly elevated in SSc skin tissues and myofibroblasts, along with significant activation of the TLR8 pathway. In vitro studies showed that overexpression or activation of TLR8 by a recombinant plasmid or VTX-2337 upregulated IL-6, IL-1β, COL I, COL III and α-SMA in skin fibroblasts. Consistently, both TLR8-siRNA and cu-cpt-8m reversed the phenotypes observed in TLR8-activating fibroblasts. Mechanistically, TLR8 induces skin fibrosis and inflammation in a manner dependent on the MAPK, NF-κB and SMAD2/3 pathways. Subcutaneous injection of cu-cpt-8m significantly alleviated BLM-induced skin inflammation and fibrosis in vivo.
Conclusion
TLR8 might be a promising therapeutic target for improving the treatment strategy for skin inflammation and fibrosis in SSc.</description><subject>Animals</subject><subject>Autoimmunity</subject><subject>Bleomycin</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Fibrosis</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Innate immunity</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Mice</subject><subject>NF-κB protein</subject><subject>Phenotypes</subject><subject>Scleroderma, Systemic - immunology</subject><subject>Scleroderma, Systemic - metabolism</subject><subject>Scleroderma, Systemic - pathology</subject><subject>Signal Transduction</subject><subject>siRNA</subject><subject>Skin</subject><subject>Skin - immunology</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Smad2 protein</subject><subject>Systemic sclerosis</subject><subject>Therapeutic targets</subject><subject>Toll-Like Receptor 8 - metabolism</subject><issn>1462-0324</issn><issn>1462-0332</issn><issn>1462-0332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkVtLw0AQhRdRbK3-A5EFX3yJ3Vt2k0cp3qAgSH0Os5tN3DaXmk2E_nu3F0V88mkG5juHmTkIXVJyS0nKp927HWro26otN9OVhVzE8giNqZAsIpyz45-eiRE6835JCIkpT07RiCspYyXUGJnF_DXBUJYdfEJvPfYr12DXFBXUwd21DYYmx4XTXeudx3qDwfQusK4p9_BupivwvQ9C7De-t7Uz2JvK7kTn6KSAytuLQ52gt4f7xewpmr88Ps_u5pFhsegjoIU2BlTM0kKCSaXmRUqUiAXj0lgGNAVhmVRJHg7TSmuWKK4sySkTogA-QTd733XXfgzW91ntvLFVBY1tB5-xRFJOYp6ygF7_QZft0DVhu4xTykXCkmRLiT1lwh2-s0W27lwN3SajJNuGkP0OITuEEGRXB_NB1zb_EX1_PQDTPdAO6_9ZfgFE-Zm7</recordid><startdate>20240503</startdate><enddate>20240503</enddate><creator>Kong, Xiangzhen</creator><creator>Jiang, Shuai</creator><creator>He, Qiuyu</creator><creator>Shi, Xiangguang</creator><creator>Pu, Weilin</creator><creator>Huang, Yan</creator><creator>Ma, Yanyun</creator><creator>Liu, Qingmei</creator><creator>Sun, Dayan</creator><creator>Huang, Delin</creator><creator>Wu, Fei</creator><creator>Li, Pengcheng</creator><creator>Tu, Wenzhen</creator><creator>Zhao, Yinhuan</creator><creator>Wang, Lei</creator><creator>Chen, Yuanyuan</creator><creator>Wu, Wenyu</creator><creator>Tang, Yulong</creator><creator>Zhao, Xiansheng</creator><creator>Zhu, Qing</creator><creator>Gao, Jian</creator><creator>Xu, Weihong</creator><creator>Shui, Xiaochuan</creator><creator>Qian, Feng</creator><creator>Wang, Jiucun</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</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>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7794-2181</orcidid></search><sort><creationdate>20240503</creationdate><title>TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis</title><author>Kong, Xiangzhen ; Jiang, Shuai ; He, Qiuyu ; Shi, Xiangguang ; Pu, Weilin ; Huang, Yan ; Ma, Yanyun ; Liu, Qingmei ; Sun, Dayan ; Huang, Delin ; Wu, Fei ; Li, Pengcheng ; Tu, Wenzhen ; Zhao, Yinhuan ; Wang, Lei ; Chen, Yuanyuan ; Wu, Wenyu ; Tang, Yulong ; Zhao, Xiansheng ; Zhu, Qing ; Gao, Jian ; Xu, Weihong ; Shui, Xiaochuan ; Qian, Feng ; Wang, Jiucun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c254t-a1fbcca7529f6ac96b3f907454236ce2a19a4e2678d146b7bb28737e0d1244fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Autoimmunity</topic><topic>Bleomycin</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Fibroblasts - metabolism</topic><topic>Fibrosis</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - metabolism</topic><topic>Innate immunity</topic><topic>Male</topic><topic>MAP kinase</topic><topic>Mice</topic><topic>NF-κB protein</topic><topic>Phenotypes</topic><topic>Scleroderma, Systemic - immunology</topic><topic>Scleroderma, Systemic - metabolism</topic><topic>Scleroderma, Systemic - pathology</topic><topic>Signal Transduction</topic><topic>siRNA</topic><topic>Skin</topic><topic>Skin - immunology</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Smad2 protein</topic><topic>Systemic sclerosis</topic><topic>Therapeutic targets</topic><topic>Toll-Like Receptor 8 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kong, Xiangzhen</creatorcontrib><creatorcontrib>Jiang, Shuai</creatorcontrib><creatorcontrib>He, Qiuyu</creatorcontrib><creatorcontrib>Shi, Xiangguang</creatorcontrib><creatorcontrib>Pu, Weilin</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>Ma, Yanyun</creatorcontrib><creatorcontrib>Liu, Qingmei</creatorcontrib><creatorcontrib>Sun, Dayan</creatorcontrib><creatorcontrib>Huang, Delin</creatorcontrib><creatorcontrib>Wu, Fei</creatorcontrib><creatorcontrib>Li, Pengcheng</creatorcontrib><creatorcontrib>Tu, Wenzhen</creatorcontrib><creatorcontrib>Zhao, Yinhuan</creatorcontrib><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Chen, Yuanyuan</creatorcontrib><creatorcontrib>Wu, Wenyu</creatorcontrib><creatorcontrib>Tang, Yulong</creatorcontrib><creatorcontrib>Zhao, Xiansheng</creatorcontrib><creatorcontrib>Zhu, Qing</creatorcontrib><creatorcontrib>Gao, Jian</creatorcontrib><creatorcontrib>Xu, Weihong</creatorcontrib><creatorcontrib>Shui, Xiaochuan</creatorcontrib><creatorcontrib>Qian, Feng</creatorcontrib><creatorcontrib>Wang, Jiucun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Rheumatology (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kong, Xiangzhen</au><au>Jiang, Shuai</au><au>He, Qiuyu</au><au>Shi, Xiangguang</au><au>Pu, Weilin</au><au>Huang, Yan</au><au>Ma, Yanyun</au><au>Liu, Qingmei</au><au>Sun, Dayan</au><au>Huang, Delin</au><au>Wu, Fei</au><au>Li, Pengcheng</au><au>Tu, Wenzhen</au><au>Zhao, Yinhuan</au><au>Wang, Lei</au><au>Chen, Yuanyuan</au><au>Wu, Wenyu</au><au>Tang, Yulong</au><au>Zhao, Xiansheng</au><au>Zhu, Qing</au><au>Gao, Jian</au><au>Xu, Weihong</au><au>Shui, Xiaochuan</au><au>Qian, Feng</au><au>Wang, Jiucun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis</atitle><jtitle>Rheumatology (Oxford, England)</jtitle><addtitle>Rheumatology (Oxford)</addtitle><date>2024-05-03</date><risdate>2024</risdate><volume>63</volume><issue>6</issue><spage>1710</spage><epage>1719</epage><pages>1710-1719</pages><issn>1462-0324</issn><issn>1462-0332</issn><eissn>1462-0332</eissn><abstract>Abstract
Objectives
Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear. The aim of this study was to explore the roles and underlying mechanisms of TLR8 in SSc.
Methods
The expression of TLR8 was analysed, based on a public dataset, and then verified in skin tissues and skin fibroblasts of SSc patients. The role of TLR8 in inflammation and fibrosis was investigated using a TLR8-overexpression vector, activator (VTX-2337), inhibitor (cu-cpt-8m), and TLR8 siRNA in skin fibroblasts. The pathogenic role of TLR8 in skin inflammation and fibrosis was further validated in a bleomycin (BLM)-induced mouse skin inflammation and fibrosis model.
Results
TLR8 levels were significantly elevated in SSc skin tissues and myofibroblasts, along with significant activation of the TLR8 pathway. In vitro studies showed that overexpression or activation of TLR8 by a recombinant plasmid or VTX-2337 upregulated IL-6, IL-1β, COL I, COL III and α-SMA in skin fibroblasts. Consistently, both TLR8-siRNA and cu-cpt-8m reversed the phenotypes observed in TLR8-activating fibroblasts. Mechanistically, TLR8 induces skin fibrosis and inflammation in a manner dependent on the MAPK, NF-κB and SMAD2/3 pathways. Subcutaneous injection of cu-cpt-8m significantly alleviated BLM-induced skin inflammation and fibrosis in vivo.
Conclusion
TLR8 might be a promising therapeutic target for improving the treatment strategy for skin inflammation and fibrosis in SSc.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>37665747</pmid><doi>10.1093/rheumatology/kead456</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-7794-2181</orcidid></addata></record> |
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| ispartof | Rheumatology (Oxford, England), 2024-05, Vol.63 (6), p.1710-1719 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE |
| subjects | Animals Autoimmunity Bleomycin Disease Models, Animal Female Fibroblasts Fibroblasts - metabolism Fibrosis Humans Inflammation Inflammation - metabolism Innate immunity Male MAP kinase Mice NF-κB protein Phenotypes Scleroderma, Systemic - immunology Scleroderma, Systemic - metabolism Scleroderma, Systemic - pathology Signal Transduction siRNA Skin Skin - immunology Skin - metabolism Skin - pathology Smad2 protein Systemic sclerosis Therapeutic targets Toll-Like Receptor 8 - metabolism |
| title | TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis |
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