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HIV-1 envelope glycoprotein 120 induces cyclooxygenase-2 expression in astrocytoma cells through a nuclear factor-κB-dependent mechanism

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Abstract

Human immunodeficiency virus-1 gp120 alters astroglial function, which compromises the function of the nearby of neuronal cells contributing to the cognitive impairment in human immunodeficiency virus-1 infection. Cyclooxygenase (COX)-2 has been involved in this process, although the intracellular pathways and second messengers involved are yet unknown. We have investigated the role of gp120-induced COX-2 in the astrocytoma human cell line U-87, and the different pathways involved in this activation. COX-2 mRNA and protein expression were detected in gp120-stimulated cells. Moreover, gp120 induces COX-2 promoter transcription. The effect of gp120 was abrogated by a neutralizing antibody against the chemokine receptor CXCR4 neutralizing antibody. Analysis of the promoter show that deletion or mutation of a proximal nuclear factor (NF)-κB site completely abrogated gp120-dependent transcription. NF-κB but neither Activating protein-1 nor nuclear factor of activated T-cells-dependent transcription was induced by gp120, as shown by reporter and electrophoretic mobility shift assays. In addition, transfection assays with the NF-κB inhibitor, IκBα, prevented gp120-mediated COX-2 induction. In contrast, there was no inhibition of COX-2 promoter transcription by expressing a dominant negative c-Jun, or nuclear factor of activated T-cells constructs. The antioxidant pyrrolidine dithiocarbamate inhibited COX-2 protein expression and COX-2 transcriptional activity induced by gp120. Thus, our results indicate that gp120 induced COX-2 transcription through NF-κB activation in astrocytoma cells.

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  1. Laboratory of Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, 28007, Madrid, Spain

    Susana Álvarez, Ma Jesús Serramía & Ma Ángeles Muñoz-Fernández

  2. Centro de Biología Molecular, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Cantoblanco, Madrid

    Susana Álvarez & Manuel Fresno

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  1. Susana Álvarez
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  2. Ma Jesús Serramía
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  4. Ma Ángeles Muñoz-Fernández
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Correspondence to Ma Ángeles Muñoz-Fernández.

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Álvarez, S., Serramía, M.J., Fresno, M. et al. HIV-1 envelope glycoprotein 120 induces cyclooxygenase-2 expression in astrocytoma cells through a nuclear factor-κB-dependent mechanism. Neuromol Med 9, 179–193 (2007). https://doi.org/10.1007/BF02685891

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