Pentoxifylline inhibits HIV-1 LTR-driven gene expression by blocking NF-kappa B action
In: Journal of acquired immune deficiency syndromes, Jg. 6 (1993-07-01), Heft 7
Online
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Zugriff:
The drug pentoxifylline (PTX) (1-(5'-oxohexyl) 3,7-dimethylxanthine) down-regulates human immunodeficiency virus (HIV-1) long terminal repeat (LTR)-directed gene expression in the human monocytic cell line U38. This effect of PTX has been tested in clinical trials. In this investigation, a similar inhibitory effect of PTX on HIV-1 LTR-driven gene expression was observed (a) in a stable transfectant of the human embryo kidney cell line 293-27-2 carrying an expression plasmid construct with the HIV-1 LTR fused to the bacterial lac Z gene, and also (b) by transient transfection of human embryo kidney cells 293 S with fusion plasmid constructs with wild-type [pHIV-LTR-chloramphenicol acetyltransferase (CAT)] or mutated (pHIV-LTR-mut-CAT) nuclear factor kappa B (NF-kappa B) motifs. In both stable and transient transfection studies, 4-beta-phorbol-12-beta-myristate-acetate (PMA)-induced or tumor necrosis factor-alpha (TNF-alpha)-induced activation of the HIV-1 LTR was correlated with a concomitant elevated level of NF-kappa B interaction with its motifs. The inducibility of HIV-1 LTR-driven gene expression by PMA or TNF-alpha in transiently transfected cells was completely eliminated by point mutations in the NF-kappa B motifs, suggesting that NF-kappa B plays a major role in the activation of the HIV-1 LTR by these agents in this cell system.(ABSTRACT TRUNCATED AT 250 WORDS)
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Pentoxifylline inhibits HIV-1 LTR-driven gene expression by blocking NF-kappa B action
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Autor/in / Beteiligte Person: | D K, Biswas ; B J, Dezube ; C M, Ahlers ; A B, Pardee |
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Zeitschrift: | Journal of acquired immune deficiency syndromes, Jg. 6 (1993-07-01), Heft 7 |
Veröffentlichung: | 1993 |
Medientyp: | unknown |
ISSN: | 0894-9255 (print) |
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