Interleukin-1 β inhibits Na+-K+ATPase activity and protein expression in cardiac myocytes

Abstract

Recent studies have shown that heart diseases are always accompanied with high levels of IL-1β and a decrease in Na+-K+ATPase concentrations. This work studies the involvement of the cytokine in the observed changes in the pump. Rats were injected intraperitoneally with 400mg of IL-1β and 4h later, the heart was isolated and a crude homogenate of the right and left ventricles was prepared and tested for Na+-K +ATPase activity and protein expression. IL-1β inhibited by around 70percent the activity of the ATPase in the left and right ventricles. This inhibition of the pump was ascribed to a decrease in its protein expression as demonstrated by western blot analysis. A dose and time response study conducted on isolated cardiac myocytes confirmed the inhibitory role of the cytokine on the ATPase and showed that IL-1β exerts its maximal down-regulatory effect at 2h and at a dose of 20ng-ml. The cytokine caused also an up-regulation of the NaKCl2 cotransporter. Both MEK and p38MAPK were shown to be involved in the signaling pathway activated by the cytokine. It can be concluded that the decrease in the Na+-K+ATPase concentration observed in heart diseases is a consequence of the accompanying high levels of IL-1β, and may be responsible for the different symptoms that accompany cardiac ischemia. © 2004 Elsevier Ltd. All rights reserved.