Effects of burn injury on myocardial signaling and cytokine secretion: possible role of PKC

Effects of burn injury on myocardial signaling and cytokine secretion: possible role of PKC. Am J Physiol Regul Integr Comp Physiol 292: R887-R896, 2007. First published September 21, 2006; doi: 10.1152/ajpregu. 00555.2006.-This study examined the effects of major burn injury on the cellular distribution of several PKC isoforms in adult rat hearts and examined the hypothesis that PKC plays a regulatory role in cardiomyocyte cytokine secretion. Burn trauma was given over 40% total body surface area in Sprague-Dawley rats. An in vitro model of burn injury included addition of burn serum, 10% by volume, to primary cardiomyocyte cultures (collagen perfusion). In vivo burn injury produced redistribution of PKC delta, PKC is an element of, and PKC alpha from the cytosol (soluble) to the membrane (particulate) component of the myocardium. This activation of the PKC isoforms was evident 2 h after burn injury and progressively increased over 24 h postburn. Addition of burn serum to isolated myocytes produced similar PKC isoform redistribution from the soluble to the particulate compartment, promoted myocyte Ca2+ and Na+ loading, and promoted robust myocyte secretion of inflammatory cytokines similar to that reported after in vivo burn injury. Pretreating cardiomyocytes with either calphostin or PKC is an element of inhibitory peptide, a potent inhibitor of PKC is an element of, prevented burn serum-related redistribution of the PKC is an element of isoform and prevented burn serum-related cardiomyocyte secretion of TNF-alpha, IL-1 beta, IL-6, and IL-10. These data suggest that the PKC is an element of isoform plays a pivotal role in myocardial inflammatory response to injury, altering cardiac function by modulating cardiomyocyte inflammatory cytokine response to injury.