IκB overexpression in cardiomyocytes prevents NF-κB translocation and provides cardioprotection in trauma

Abstract

This study examined the effects of either IκBα overexpression (transgenic mice) or N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) administration (proteosome inhibitor in wild-type mice) on cardiomyocyte secretion of tumor necrosis factor-α (TNF-α) and on cardiac performance after burn trauma. Transgenic mice were divided into four experimental groups. IκBα overexpressing mice were given a third-degree scald burn over 40% of the total body surface area or wild-type littermates were given either a scald or sham burn to provide appropriate controls. Pharmacological studies included ALLN (20 mg/kg) administration in either burned wild-type mice or wild-type shams. Burn trauma in wild-type mice promoted nuclear factor-κB (NF-κB) nuclear translocation, cardiomyocyte secretion of TNF-α, and impaired cardiac performance. IκBα overexpression or ALLN treatment of burn trauma prevented NF-κB activation in cardiac tissue, prevented cardiomyocyte secretion of TNF-α, and ablated burn-mediated cardiac contractile dysfunction. These data suggest that NF-κB activation and inflammatory cytokine secretion play a significant role in postburn myocardial abnormalities.