title: Tumor necrosis factor alpha leads to increased cell surface expression of CXCR4 in SK-N-MC cells.
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)-alpha, CXCR4, the alpha chemokine receptor, and three HIV isolates, including the T-tropic viruses, HIV-1(MN) and HIV-1(IIIB), and the dual tropic virus, HIV-1(89.6). The authors show by flow cytometry that treatment of differentiated SK-N-MC cells with TNF-alpha 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-alpha 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-alpha. Together these results suggest that TNF-alpha 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-alpha contributes to the pathogenesis of HIV-associated brain injury.
authors.affiliation: Department of Pediatrics, Division of Neurology, University of Göttingen, Göttingen, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostasy
authors.forename: Gullue
authors.initials: G
authors.lastname: Gorgun
authors.forename: Yelena
authors.initials: Y
authors.lastname: Kleyner
authors.forename: Anthony
authors.initials: A
authors.lastname: Garcia
authors.forename: Michael
authors.initials: M
authors.lastname: Kramer
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Melanson
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Mathys
authors.forename: Constantin
authors.initials: C
authors.lastname: Yiannoutsos
authors.forename: Paul R
authors.initials: PR
authors.lastname: Skolnik
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Navia
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000821:virology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha