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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
1994-1-4
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pubmed:abstractText |
Human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-regulated gene expression is stimulated independently by the cellular trans-activator NF-kappa B and the viral protein Tat. Noncytotoxic concentrations of the drug pentoxifylline (PTX) inhibited interaction of NF-kappa B with its motif and the stimulation of HIV-1 LTR-driven gene expression in Jurkat cells. Tat protein (from a cotransfected Tat-expression vector) also induced activation of HIV-1 LTR-driven gene expression. This activation was unaffected by PTX when NF-kappa B sites in the HIV-1 LTR were mutated, suggesting that this drug does not directly influence Tat function, which, however, was inhibited by the Tat-inhibitor Ro 24-7429. Transient reporter gene expression regulated by HIV-1 LTR with wild-type NF-kappa B motifs in the presence of Tat protein was 10- to 60-fold higher than in the presence of either of the trans-activators alone, demonstrating superactivation of HIV-1 LTR by the concerted action of both the trans-activators. Treatment of cells with either PTX or Ro 24-7429 inhibited this superactivation of the HIV-1 LTR. The inhibitory effect of these two drugs in combination, at concentrations that alone did not significantly influence viral promoter activity, was far more than additive. A cooperative action of PTX (NF-kappa B inhibitor) and Ro 24-7429 (Tat inhibitor) on HIV-1 LTR-regulated gene expression is suggested. Concentrations of the drugs that induced maximum inhibition of HIV-1 LTR through their cooperative action are far below cytotoxic levels. Thus, the combination of these two inhibitors could be very effective for anti-HIV therapy.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-1406488,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-1431144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-1540410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-1583734,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-1583736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-1721310,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-1763331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-1907460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-2016766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-2062653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-2112750,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-2263644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-2795721,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-2830675,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-2988790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-3031512,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-3059495,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-3096580,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-6275366,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-6278479,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-6828386,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-8341644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-8446597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-8449662,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8248210-8509980
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
90
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11044-8
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8248210-Antiviral Agents,
pubmed-meshheading:8248210-Benzodiazepines,
pubmed-meshheading:8248210-Cell Line,
pubmed-meshheading:8248210-Drug Synergism,
pubmed-meshheading:8248210-Gene Expression Regulation, Viral,
pubmed-meshheading:8248210-Gene Products, tat,
pubmed-meshheading:8248210-HIV Long Terminal Repeat,
pubmed-meshheading:8248210-HIV-1,
pubmed-meshheading:8248210-Humans,
pubmed-meshheading:8248210-NF-kappa B,
pubmed-meshheading:8248210-Pentoxifylline,
pubmed-meshheading:8248210-Pyrroles,
pubmed-meshheading:8248210-tat Gene Products, Human Immunodeficiency Virus
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pubmed:year |
1993
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pubmed:articleTitle |
Cooperative inhibition of NF-kappa B and Tat-induced superactivation of human immunodeficiency virus type 1 long terminal repeat.
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pubmed:affiliation |
Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Boston, MA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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