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

Chayanit Chaweewannakorn, Masahiro Tsuchiya, Masashi Koide, Hiroyasu Hatakeyama, Yukinori Tanaka, Shinichirou Yoshida, Shunji Sugawara, Yoshihiro Hagiwara, Keiichi Sasaki, Makoto Kanzaki

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)R90-R103,
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume315
Issue number1
DOIs
Publication statusPublished - 2018 Jul 2

Keywords

  • Actin remodeling
  • Fusion error
  • Il-1
  • Il-1-deficient mice
  • Muscle regeneration
  • Myoblasts
  • Satellite cells

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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