Functional capability of IL-15-Akt signaling in the denervated muscle

Introduction: Denervation of skeletal muscles results in timely muscle-T cell cross-talk, but the mechanistic details of the orchestrated local circuits, as well as the potential regulatory link to the muscular function have not been established. Methods: We used a combination of techniques to measure: (i) timely expression of IL-1 beta-ERK1/2 and IL-15-Akt signaling and (ii) celluar events controlled by IL-15-Akt signaling. Techniques included gastrocnemius strip, satellite cell culture, real time PCR, immunoprecipitation, Western blotting and subcellular fractionation. Besides that, muscle cell survival was determined by MTT assay. Results: We found that there were two events: rapid IL-1 beta-ERK1/2 (1 day) and the later IL-15-Akt signaling (7 day) were selectively triggered by sciatic nerve injury. IL-15-Akt signaling was mostly targeted on CD2 phosphorylation and strengthened CD2-CD48 adhesion within gastrocnemius lipid rafts, in the same time, it exerted a restriction on TAB2 via miR155 pathway, thereby prevented muscle cell from inflammatory damage. Conclusions: Our results suggested that IL-15-Akt signaling harbored the complex signals for muscle-T cell interaction, the regulatory networks have significant potential for the restriction on IL-1 beta inflammatory signaling. These results are likely to provide new insights into the therapy of neuromuscular injury. (c) 2012 Elsevier Ltd. All rights reserved.