title: Time-course analysis of injured skeletal muscle suggests a critical involvement of ERK1/2 signaling in the acute inflammatory response.
abstract: BACKGROUND
  The coupling and timing of pro- and anti-inflammatory processes in skeletal muscle injury is poorly understood. We investigated the temporal response and regulated processes of extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, and IkappaB kinase (IKK) α/β signaling pathways after traumatic injury.
  
  
  METHODS
  Traumatic freeze injury was delivered to the tibialis anterior (TA) muscle in C57BL/6J mice, and injured and uninjured TA muscles were analyzed 3-72 h into the recovery period.
  
  
  RESULTS
  Significant increases in pro-inflammatory cytokine transcription accompanied IKKβ phosphorylation, robust ERK pathway activation, and reduced heat shock protein (Hsp) protein expression at 3-24 h. At 24 h, ERK activation was abolished concomitantly with a significant increase in mitogen-activated protein kinase phosphatase-1 (MKP-1). After 24 h, cytokine transcription along with ERK1/2 and IKKβ phosphorylation remained suppressed, whereas Hsp protein expression rose to significant levels by 72 h and associated with IKKβ.
  
  
  CONCLUSIONS
  Results indicate a bimodal regulation of ERK1/2 in acute inflammation in which it is supportive from 3 to 24 h, and suppressive from 24 to 72 h.
authors.affiliation: U.S. Army Research Institute of Environmental Medicine, 42 Kansas Street, Building 42, Natick, Massachusetts 01760, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Szelenyi
authors.forename: Maria L
authors.initials: ML
authors.lastname: Urso
mesh_terms: D000818:Animals; D015153:Blotting, Western; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006614:Hindlimb / Q000293:injuries; D051550:I-kappa B Kinase / Q000378:metabolism; D047468:Immunoprecipitation; D007249:Inflammation / Q000503:physiopathology*; D016753:Interleukin-10 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000293:injuries* / Q000503:physiopathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D016207:Cytokines; D006360:Heat-Shock Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D016753:Interleukin-10; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2