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 pro-inflammatory factors including IL-6 and delayed increase of PAX7-positive satellite cells post-injury as 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.
doi: 10.1152/ajpregu.00310.2017.
Chaweewannakorn C, Tsuchiya M, Koide M, Hatakeyama H, Tanaka Y, Yoshida S, Sugawara S, Hagiwara Y, Sasaki K, Kanzaki M.
