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

Patel, H; Yong, C; Navi, A; Shaw, SG; Shiwen, X; Abraham, D; Baker, DM; (2019) Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes. Vascular Medicine , 24 (4) pp. 295-305. 10.1177/1358863X19843180. Green open access

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Abstract

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.

Type: Article
Title: Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/1358863X19843180
Publisher version: http://doi.org/10.1177/1358863X19843180
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Toll-like receptors, critical limb ischemia (CLI), inflammation, peripheral artery disease (PAD), skeletal muscle
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10074794
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