Tumor Necrosis Factor-Alpha Induced VCAM-l Expression is Inhibited by High Density Lipoprotein in Human Astroglioma Cells

Abstract

Astrocytes, the major glial cells in the central nervous system (CNS), can express vascular cell adhesion molecule-l (YCAM-l) in response to cytokines, such as TNF-a. In CNS, an increased YCAM-l expression may contribute to inflammatory processes. We, in the present study, have examined the effect of human plasma High Density Lipoproteins (HDL) and other lipoproteins on YCAM-l expression in astroglioma cells since astrocytes secrete HDL-like lipoprotein particles which contain apo E and cholesterol, phospholipid. The exposure of astroglioma cells to the major plasma lipoprotein fractions (YLDL, LDL and HDL) had no effect on the YCAM-l expression. However, TNF-a-induced YCAM-l was inhibited by HDL in a dose-dependent manner, but not by YLDL or LDL. The inhibitory effect of HDL on TNF-α-induced YCAM-l was reversed by the inclusion of Apo A-I antibody, the major apolipoprotein of HDL, demonstrating the specificity of this response. Reconstituted HDL (discoidal complex of apo HDL and DMPC), but not apo HDL or DMPC, was effective in suppressing the YCAM-l expression. RNase protection assay (RPA) revealed that TNF-ainduced YCAM-l mRNA expression was markedly inhibited by HDL (500㎍ cholesterol/㎖). These results indicate that HDL-like particles in the CNS may function as an immunosuppressive molecule in pathologic conditions of CNS.