Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes
Critical limb ischemia (CLI) is associated with skeletal muscle damage. However, the pathophysiology of the muscle damage is poorly understood. Toll-like receptors (TLR) have been attributed to play a role in ischemia-induced tissue damage but their role in skeletal muscle damage in CLI is unknown....
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| Veröffentlicht in: | Vascular medicine (London, England) England), 2019-08, Vol.24 (4), p.295-305 |
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| creator | Patel, Hemanshu Yong, Cissy Navi, Ali Shaw, Sidney G Shiwen, Xu Abraham, David Baker, Daryll M Tsui, Janice CS |
| description | Critical limb ischemia (CLI) is associated with skeletal muscle damage. However, the pathophysiology of the muscle damage is poorly understood. Toll-like receptors (TLR) have been attributed to play a role in ischemia-induced tissue damage but their role in skeletal muscle damage in CLI is unknown. TLR2 and TLR6 expression was found to be upregulated in skeletal muscle of patients with CLI. In vitro, ischemia led to upregulation of TLR2 and TLR6 by myotubes, and activation of the downstream TLR signaling pathway. Ischemia-induced activation of the TLR signaling pathway led to secretion of the pro-inflammatory cytokine interleukin-6 and muscle apoptosis, which were abrogated by neutralising TLR2 and TLR6 antibodies. Our study demonstrates that TLR2 and TLR6 are upregulated in ischemic muscle and play a role in ischemia-induced muscle damage. Thus, manipulating the TLR pathway locally may be of potential therapeutic benefit. |
| doi_str_mv | 10.1177/1358863X19843180 |
| format | Article |
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However, the pathophysiology of the muscle damage is poorly understood. Toll-like receptors (TLR) have been attributed to play a role in ischemia-induced tissue damage but their role in skeletal muscle damage in CLI is unknown. TLR2 and TLR6 expression was found to be upregulated in skeletal muscle of patients with CLI. In vitro, ischemia led to upregulation of TLR2 and TLR6 by myotubes, and activation of the downstream TLR signaling pathway. Ischemia-induced activation of the TLR signaling pathway led to secretion of the pro-inflammatory cytokine interleukin-6 and muscle apoptosis, which were abrogated by neutralising TLR2 and TLR6 antibodies. Our study demonstrates that TLR2 and TLR6 are upregulated in ischemic muscle and play a role in ischemia-induced muscle damage. 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However, the pathophysiology of the muscle damage is poorly understood. Toll-like receptors (TLR) have been attributed to play a role in ischemia-induced tissue damage but their role in skeletal muscle damage in CLI is unknown. TLR2 and TLR6 expression was found to be upregulated in skeletal muscle of patients with CLI. In vitro, ischemia led to upregulation of TLR2 and TLR6 by myotubes, and activation of the downstream TLR signaling pathway. Ischemia-induced activation of the TLR signaling pathway led to secretion of the pro-inflammatory cytokine interleukin-6 and muscle apoptosis, which were abrogated by neutralising TLR2 and TLR6 antibodies. Our study demonstrates that TLR2 and TLR6 are upregulated in ischemic muscle and play a role in ischemia-induced muscle damage. Thus, manipulating the TLR pathway locally may be of potential therapeutic benefit.</description><subject>Activation</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Damage</subject><subject>Immune system</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Interleukins</subject><subject>Ischemia</subject><subject>Muscles</subject><subject>Musculoskeletal system</subject><subject>Myotubes</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Skeletal muscle</subject><subject>TLR2 protein</subject><subject>Toll-like receptors</subject><subject>Vitamin E</subject><issn>1358-863X</issn><issn>1477-0377</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kM1LwzAYxoMobk7vniTgxUs1X03Sowy_YOBlggehpO1b7ZY2M2kP--_N3FQYeMrH83ue9-VB6JySa0qVuqE81VryV5ppwakmB2hMhVIJ4UodxnuUk40-QichLAghSmb0GI04JVpExxi9zZ21iW2WgD2UsOqdD5hh01VY4haqxvSAzcpFITTh-7_pamva1vSN6-IDN6H8gLYpcViChd5Y3K5dPxQQTtFRbWyAs905QS_3d_PpYzJ7fnia3s6SUhDVJzUtK6J1VqhaQMUyygyI1BBpNFNGSaM0FKBLrjSrJKllzcEwWaWayRRKwifoapu78u5zgNDnbVwKrDUduCHkjHFGmJBMRvRyD124wXdxu0ilQqQkzXikyJYqvQvBQ52vfNMav84pyTfN5_vNR8vFLngoYm-_hp-qI5BsgWDe4W_qv4FfoKCKxQ</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Patel, Hemanshu</creator><creator>Yong, Cissy</creator><creator>Navi, Ali</creator><creator>Shaw, Sidney G</creator><creator>Shiwen, Xu</creator><creator>Abraham, David</creator><creator>Baker, Daryll M</creator><creator>Tsui, Janice CS</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4876-5139</orcidid></search><sort><creationdate>20190801</creationdate><title>Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes</title><author>Patel, Hemanshu ; Yong, Cissy ; Navi, Ali ; Shaw, Sidney G ; Shiwen, Xu ; Abraham, David ; Baker, Daryll M ; Tsui, Janice CS</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c407t-f1cd0889b7f4ed2912ae45a06a827a76a78ebe8c3782d60f6f3ea26d58265ec03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Activation</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Damage</topic><topic>Immune system</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Interleukins</topic><topic>Ischemia</topic><topic>Muscles</topic><topic>Musculoskeletal system</topic><topic>Myotubes</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Skeletal muscle</topic><topic>TLR2 protein</topic><topic>Toll-like receptors</topic><topic>Vitamin E</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Patel, Hemanshu</creatorcontrib><creatorcontrib>Yong, Cissy</creatorcontrib><creatorcontrib>Navi, Ali</creatorcontrib><creatorcontrib>Shaw, Sidney G</creatorcontrib><creatorcontrib>Shiwen, Xu</creatorcontrib><creatorcontrib>Abraham, David</creatorcontrib><creatorcontrib>Baker, Daryll M</creatorcontrib><creatorcontrib>Tsui, Janice CS</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Vascular medicine (London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Patel, Hemanshu</au><au>Yong, Cissy</au><au>Navi, Ali</au><au>Shaw, Sidney G</au><au>Shiwen, Xu</au><au>Abraham, David</au><au>Baker, Daryll M</au><au>Tsui, Janice CS</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes</atitle><jtitle>Vascular medicine (London, England)</jtitle><addtitle>Vasc Med</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>24</volume><issue>4</issue><spage>295</spage><epage>305</epage><pages>295-305</pages><issn>1358-863X</issn><eissn>1477-0377</eissn><abstract>Critical limb ischemia (CLI) is associated with skeletal muscle damage. 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| source | SAGE Journals Online; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Activation Antibodies Apoptosis Damage Immune system Inflammation Interleukin 6 Interleukins Ischemia Muscles Musculoskeletal system Myotubes Proteins Receptors Signal transduction Signaling Skeletal muscle TLR2 protein Toll-like receptors Vitamin E |
| title | Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes |
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