IRAK contributes to burn-triggered myocardial contractile dysfunction.
Major burn injury causes myocardial contractile dysfunction, but the molecular basis of this physiological response is incompletely understood. Previous studies demonstrated a role for the interleukin-1 receptor-associated kinase (IRAK) in the cardiac response to acute lipopolysaccharide administration as well as congestive heart failure. In this study, we examined the contribution of IRAK to burn-mediated cardiac responses. After burn injury, hearts from wild-type and IRAK-deficient mice were compared for intracellular signaling pathway activation and contractile function. IRAK-deficient hearts showed impaired activation of kinases that function downstream of IRAK and were partially protected against burn-induced contractile dysfunction. The findings demonstrate that IRAK and the Toll/interleukin-1 pathways participate in the response to large body surface area burns that leads to impaired cardiac contractility.
Thomas
James A
JA
Department of Pediatrics, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. James.Thomas@UTSouthwestern.edu
Tsen
May F
MF
White
D Jean
DJ
Horton
Jureta W
JW
D000818:Animals; D002056:Burns / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000503:physiopathology; D053592:Interleukin-1 Receptor-Associated Kinases; D007425:Intracellular Membranes / Q000502:physiology; D008297:Male; D051379:Mice; D009200:Myocardial Contraction; D011494:Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D012016:Reference Values; D015398:Signal Transduction
D002316:Cardiotonic Agents; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases