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

Kevin Rostasy, Gullue Gorgun, Yelena Kleyner, Anthony Garcia, Michael Kramer, Suzanne M. Melanson, Jean Marie Mathys, Constantin Yiannoutsos, Paul R. Skolnik, Bradford A. Navia

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 apoptotic effects of HIV by increasing the cell surface expression of CXCR4 and thus identify another mechanism by which TNF-α contributes to the pathogenesis of HIV-associated brain injury.

Original languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalJournal of neurovirology
Volume11
Issue number3
DOIs
StatePublished - Jul 1 2005

Keywords

  • AIDS
  • CXCR4
  • Chemokine receptors
  • HIV dementia
  • TNF-α

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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    Rostasy, K., Gorgun, G., Kleyner, Y., Garcia, A., Kramer, M., Melanson, S. M., Mathys, J. M., Yiannoutsos, C., Skolnik, P. R., & Navia, B. A. (2005). Tumor necrosis factor alpha leads to increased cell surface expression of CXCR4 in SK-N-MC cells. Journal of neurovirology, 11(3), 247-255. https://doi.org/10.1080/13550280590952763