Thus both, the increased MICA/B expression on HL target cells and the enhanced TNFalpha secretion, might contribute to the improved effector cell killing activity in response to LBH589 treatment. We and others established that LBH589 induced a dose-dependent decrease of cell viability in the HL cell lines L428, L540 and KM-H2 but also in peripheral blood mononuclear cells, albeit to a lesser extent in the latter. Furthermore, autophagy was induced by LBH589, since HL cell lysates showed a significant increase for the autophagy marker LC3II in Western Blot analysis. Cells also formed intracellular, LC3-positve punctae in immunocytochemistry. These data are in line with previous studies of LBH589 inducing apoptosis and autophagy in HL cell lines and may further contribute to an enhanced A 286982 susceptibility against effector cell killing. HDL is a multi-functional particle that participates in a variety of athero-protective roles that include promotion of endothelial homeostasis and inhibition of monocyte adhesion. Arguably, HDL��s most important function is in preventing cholesterol accumulation in the vessel wall via the reverse cholesterol transport pathway, where HDL is responsible for transporting cholesterol from peripheral tissues to the liver for excretion. Delivery of cholesterol into the liver occurs by HDL binding to scavenger receptor class B type I, a highly glycosylated cell-surface receptor that mediates selective uptake of HDL-cholesteryl esters into the cell. It has been suggested that HDL and SR-BI must be properly aligned in order to achieve efficient CE transfer, a process that requires the extracellular domain of SR-BI. SR-BI is highly expressed in the liver and steroidogenic tissues, and is also present in macrophages where it has been suggested to play a role in free cholesterol efflux to HDL particles. Altogether, the SR-BI/HDL interaction plays a crucial role in whole body cholesterol flux. Oxidative AC 265347 stress plays a central role in the pathophysiology of atherosclerosis by inducing dyslipidemia, atheroma formation and endothelial dysfunction. The role of oxidized low density lipoproteins in promoting atherogenesis is well-established and has been studied for decades. More recently, the oxidation of HDL by oxidative stress has been garnering much attention as we shift towards the concept that HDL function and cholesterol flux may be better predictors of cardiovascular risk than HDL-cholesterol levels. Under oxidative stress, HDL is susceptible to modification by a large cohort of oxidants present in vivo, such as metal ions, reactive aldehydes, and other products of endogenous oxidants, as well as environmental factors, such as poor diet and tobacco use. These modifications to HDL may reduce or eliminate HDL��s athero-protective effects, leading to a ��dysfunctional�� particle. HDL proteins can be modified by the highly reactive ��,��-unsaturated aldehyde, acrolein.