Ethanol strongly potentiates apoptosis induced by HIV-1 proteins in primary human brain microvascular endothelial cells

Abstract

Ethanol may have significant effects on human immunodeficiency virus type I (HIV-1) pathogenesis in vivo. As such, the effects of ethanol treatment were studied on the proapoptotic potential of various HIV-1 proteins in primary isolated human brain microvascular endothelial cells (MVECs), a major cellular component of the blood-brain barrier. Low-passage primary brain MVECs were treated with recombinant HIV-1 proteins Nef, Vpr, Tat and gp120 proteins from X4, R5, and X4R5 viral strains, with and without ethanol at various relevant concentrations. The apoptotic potential of each HIV-1 protein with and without ethanol was compared with cells treated with ethanol alone or GST protein as a control, under similar conditions. Specific HIV-1 proteins induced apoptosis in primary isolated human brain MVECs, which was potentiated on treatment with 0.1 and 0.3% (v/v) ethanol. Cotreatment with ethanol and specific HIV-1 proteins showed enhanced lactate dehydrogenase release, compared with MVECs treated with ethanol alone. The presence of ethanol in in vitro culture medium also enhanced HIV-1 protein-mediated tumor necrosis factor-alpha production, compared with cells treated with ethanol alone or GST protein. Thus, these studies demonstrate ethanol's potential for inducing apoptosis of human MVECs with relevant HIV-1-specific proteins and suggest a potential synergistic effect in augmenting HIV-1 neuroinvasion and neuropathogenesis in vivo.