title: Functional capability of IL-15-Akt signaling in the denervated muscle.
abstract: BACKGROUND
  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-1β-ERK1/2 and IL-15-Akt signaling and (ii) cellular 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-1β-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-1β inflammatory signaling. These results are likely to provide new insights into the therapy of neuromuscular injury.
authors.affiliation: Department of Integrative Medicine and Neurobiology, National Key Lab of Medical Neurobiology, Institute of Brain Sciences, Fudan University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Hanwei
authors.initials: H
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism; D000071178:CD48 Antigen; D019409:Interleukin-15 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D035683:MicroRNAs; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries / Q000601:surgery; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D018801:CD2 Antigens; D000071178:CD48 Antigen; C000604067:Cd48 protein, rat; D019409:Interleukin-15; D053583:Interleukin-1beta; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3