Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes

Patel, Hemanshu; Yong, Cissy; Navi, Ali; Shaw, Sidney G; Shiwen, Xu; Abraham, David; Baker, Daryll M; Tsui, Janice CS

doi:10.1177/1358863x19843180

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Journal article

Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes

Patel, Hemanshu ORCID Division of Surgery & Interventional Science, University College London, Royal Free Campus, London, UK
Yong, Cissy Division of Surgery & Interventional Science, University College London, Royal Free Campus, London, UK
Navi, Ali Division of Surgery & Interventional Science, University College London, Royal Free Campus, London, UK
Shaw, Sidney G Department of Clinical Experimental Research, University of Bern, Bern, Switzerland
Shiwen, Xu Centre for Rheumatology & Connective Tissue Disease, University College London, Royal Free Campus, London, UK
Abraham, David Centre for Rheumatology & Connective Tissue Disease, University College London, Royal Free Campus, London, UK
Baker, Daryll M Division of Surgery & Interventional Science, University College London, Royal Free Campus, London, UK
Tsui, Janice CS Division of Surgery & Interventional Science, University College London, Royal Free Campus, London, UK

2019-5-14

Published in:

Vascular Medicine. - SAGE Publications. - 2019, vol. 24, no. 4, p. 295-305

Cardiology and Cardiovascular Medicine

English 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.

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English

Open access status

green

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DOI 10.1177/1358863x19843180
ISSN 1358-863X

Persistent URL

https://sonar.ch/global/documents/264024

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