High density lipoproteins (HDL) profoundly inhibit TNF-stimulated sphingosine kinase activity in endothelial cells, decreasing sphingosine 1-phosphate production and adhesion protein expression.
Does HDL inhibit TNF-stimulated sphingosine kinase activity and adhesion protein expression in endothelial cells?
HDL protects against atherosclerosis by inhibiting the sphingosine kinase signaling pathway and enhancing cellular ceramide levels in endothelial cells.
The ability of high density lipoproteins (HDL) to inhibit cytokine-induced adhesion molecule expression has been demonstrated in their protective function against the development of atherosclerosis and associated coronary heart disease. A key event in atherogenesis is endothelial activation induced by a variety of stimuli such as tumor necrosis factor-alpha (TNF), resulting in the expression of various adhesion proteins. We have recently reported that sphingosine 1-phosphate, generated by sphingosine kinase activation, is a key molecule in mediating TNF-induced adhesion protein expression. We now show that HDL profoundly inhibit TNF-stimulated sphingosine kinase activity in endothelial cells resulting in a decrease in sphingosine 1-phosphate production and adhesion protein expression. HDL also reduced TNF-mediated activation of extracellular signal-regulated kinases and NF-kappaB signaling cascades. Furthermore, HDL enhanced the cellular levels of ceramide which in turn inhibits endothelial activation. Thus, the regulation of sphingolipid signaling in endothelial cells by HDL provides a novel insight into the mechanism of protection against atherosclerosis.
Xia et al. (1999) studied Atherosclerosis. High density lipoproteins (HDL) was evaluated on TNF-stimulated sphingosine kinase activity and adhesion protein expression. High density lipoproteins (HDL) profoundly inhibit TNF-stimulated sphingosine kinase activity in endothelial cells, decreasing sphingosine 1-phosphate production and adhesion protein expression.