Transactivation of human immunodeficiency virus type 1 long terminal repeats by cell surface tumor necrosis factor alpha.
Tumor necrosis factor alpha (TNF-alpha) is expressed in secreted and cell surface (csTNF-alpha) forms by activated monocytic and T cells. In this report, we demonstrate that csTNF-alpha may predominantly regulate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) activation in the promonocytic cell line U937 and in the Epstein-Barr virus-transformed B-cell line BH1. Anti-TNF-alpha antibody suppressed both the constitutive expression of the HIV-1 LTR in BH1 cells and the expression induced by phorbol 12-myristate 13-acetate in U937 cells. This suppression was found to be mediated via csTNF-alpha. No correlation between the HIV-1 LTR activation and the secretion of TNF-alpha was evident in these cell lines. Suppression of TNF-alpha secretion by cyclosporin A or by a serine protease inhibitor did not suppress the HIV-1 LTR activation. These observations suggest a novel biological role for csTNF-alpha in the immunopathogenesis of AIDS.
Tadmori
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W
Department of Molecular Oncology, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121.
Mondal
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D
Tadmori
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Prakash
O
O
D002460:Cell Line; D005434:Flow Cytometry; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate