Roles of IL-1α/β in regeneration of cardiotoxin-injured muscle and satellite cell function

  • Chayanit Chaweewannakorn
    Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
  • Masahiro Tsuchiya
    Department of Nursing, Tohoku Fukushi University, Sendai, Japan
  • Masashi Koide
    Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
  • Hiroyasu Hatakeyama
    Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan
  • Yukinori Tanaka
    Division of Oral Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan
  • Shinichirou Yoshida
    Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
  • Shunji Sugawara
    Division of Oral Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan
  • Yoshihiro Hagiwara
    Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
  • Keiichi Sasaki
    Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
  • Makoto Kanzaki
    Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan

書誌事項

公開日
2018-07-01
資源種別
journal article
DOI
  • 10.1152/ajpregu.00310.2017
公開者
American Physiological Society

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説明

<jats:p>Skeletal muscle regeneration after injury is a complex process involving interactions between inflammatory microenvironments and satellite cells. Interleukin (IL)-1 is a key mediator of inflammatory responses and exerts pleiotropic impacts on various cell types. Thus, we aimed to investigate the role of IL-1 during skeletal muscle regeneration. We herein show that IL-1α/β-double knockout (IL-1KO) mice exhibit delayed muscle regeneration after cardiotoxin (CTX) injection, characterized by delayed infiltrations of immune cells accompanied by suppressed local production of proinflammatory factors including IL-6 and delayed increase of paired box 7 (PAX7)-positive satellite cells postinjury compared with those of wild-type (WT) mice. A series of in vitro experiments using satellite cells obtained from the IL-1KO mice unexpectedly revealed that IL-1KO myoblasts have impairments in terms of both proliferation and differentiation, both of which were reversed by exogenous IL-1β administration in culture. Intriguingly, the delay in myogenesis was not attributable to the myogenic transcriptional program since MyoD and myogenin were highly upregulated in IL-1KO cells, instead appearing, at least in part, to be due to dysregulation of cellular fusion events, possibly resulting from aberrant actin regulatory systems. We conclude that IL-1 plays a positive role in muscle regeneration by coordinating the initial interactions among inflammatory microenvironments and satellite cells. Our findings also provide compelling evidence that IL-1 is intimately engaged in regulating the fundamental function of myocytes.</jats:p>

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