Tumor necrosis factor alpha leads to increased cell surface expression of CXCR4 in SK-N-MC cells.

Both host and viral factors play an important role in the pathogenesis of human immunodeficiency virus (HIV)-associated bran injury. In this study, the authors examined the interactions between tumor necrosis factor (TNF)-α, CXCR4, the alpha chemokine receptor, and three HIV isolates, including the T-tropic viruses, HIV-1MN and HIV-1IIIB, and the dual tropic virus, HIV-189.6. The authors show by flow cytometry that treatment of differentiated SK-N-MC cells with TNF-α induces a significant increase in the cell surface expression of CXCR4 in a time- and dose-dependent manner. The effect is partly regulated at the level of transcription. To assess the biological significance of this finding, we show that TNF-α potentiates the ability of the above mentioned HIV isolates to induce neuronal apoptosis and that the effect is significantly reduced by pretreating cells with monoclonal antibodies to either CXCR4 and TNF-α. Together these results suggest that TNF-α may render neuronal cells vulnerable to the apoptoti...