Role for toll-like receptor 3 in muscle regeneration after cardiotoxin injury

• Published in: Muscle & nerve 2011-05, Vol.43 (5), p.733-740
• Main Authors: Mathes, Allison L., Lafyatis, Robert
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; cardiotoxin; Cardiotoxins - toxicity; cytokines; Fundamental and applied biological sciences. Psychology; Immunity, Innate - drug effects; Inflammation Mediators - physiology; Mice; Mice, Knockout; muscle regeneration; Muscle, Skeletal - drug effects; Muscle, Skeletal - injuries; Muscle, Skeletal - pathology; Regeneration - drug effects; Regeneration - physiology; Striated muscle. Tendons; toll-like receptor 3; Toll-Like Receptor 3 - physiology; type 1 interferon; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.21959

Introduction: Sterile tissue injury induces an inflammatory response involving cytokines that have crucial roles in the tissue repair that follows. Methods: MyH3 and type 1 interferon (IFN) were assessed by qPCR after cardiotoxin (CTX)‐induced muscle injury. Results: CTX‐induced injury increased expression of IFN‐regulated genes, IFIT1 and MX‐2, which was blocked in type 1 IFN receptor (IFNR)‐deficient mice. However, IFNR‐deficient mice showed no significant differences in muscle regeneration as assessed by MyH3 expression. MyH3 was significantly reduced in TLR3‐deficient but not MyD88‐deficient mice. TLR3‐deficient mice also showed altered expression of proinflammatory cytokines, IL‐6, IL‐1β, and TNF‐α. Conclusions: CTX‐induced muscle injury increased markers of innate immune activation, but blocking type 1 IFN signaling had no effect on muscle regeneration. Taken together, these results suggest a role for TLR3, and perhaps other innate immune signals, in the inflammatory response to CTX‐induced muscle injury and consequent muscle regeneration. Muscle Nerve, 2011