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M94A3310.TXT
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1994-10-25
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Document 3310
DOCN M94A3310
TI Regulation of HIV-1 gene expression in monocyte-derived macrophages.
DT 9412
AU Moelans I; de Vos M; de Graaf L; Nottet H; Visser MR; Verhoef J;
Eijkman-Winkler Institute of Medical Microbiology, Utrecht, The;
Netherlands.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):105 (abstract no. PA0039). Unique
Identifier : AIDSLINE ICA10/94369265
AB OBJECTIVE: N-acetyl-L-cysteine (NAC), phorbol 12-myristate (PMA) and
lipopolysaccharide (LPS), have an opposite effect on HIV-1 production in
monocyte-derived macrophages (MDM) when compared with their effect in
lymphocytes. We have investigated if the different effects in
lymphocytes and MDM are due to a difference in regulation of gene
expression in both cell types. METHODS: Regulation of whole virus
production in MDM was assayed by p24 ELISA. To localize putative NAC,
PMA and LPS responsive sequences within the HIV-1 LTR, transient
transfection experiments were performed with plasmids in which LTR
sequences direct the expression of the bacterial chloramphenicol
acetyltransferase (CAT) gene. Electrophoretic mobility shift assays were
applied to study specific binding of cellular transcription factors with
regulatory elements in the HIV-1 LTR in the presence of NAC, PMA and
LPS. RESULTS: In MDM HIV-1 replication, as determined by p24 production,
is increased in the presence of NAC, in contrast to the effect of this
drug on HIV-1 replication in lymphocytes. In lymphocytes HIV-1
replication is increased in the presence of PMA and LPS, whereas these
stimuli lead to a down-regulation of the HIV-1 production in MDM. In the
case of NAC, comparable results were obtained when MDM and lymphocytes
(Jurkat cells) were transiently transfected with LTR-CAT constructs and
CAT activity was measured. Interestingly, electrophoretic mobility shift
assays revealed a (concentration-dependent) increased binding of NF-kB
like protein(s) to kB sites of HIV-1 LTR in nuclear extracts of MDM upon
NAC treatment. CONCLUSIONS: Overall, the results indicate that the
transcription factor NF-kB is probably involved in the up-regulation of
HIV-1 gene expression by NAC in MDM. Our studies also emphasize the
importance of comparing the effects of enhancers and inhibitors of HIV-1
replication in different human celltypes.
DE Acetylcysteine/PHARMACOLOGY Cell Line Chloramphenicol
Acetyltransferase/GENETICS Comparative Study *Gene Expression
Regulation, Viral/DRUG EFFECTS Human HIV Long Terminal Repeat
HIV-1/DRUG EFFECTS/*GENETICS/PHYSIOLOGY
Lipopolysaccharides/PHARMACOLOGY Macrophages/DRUG EFFECTS/*MICROBIOLOGY
Monocytes/DRUG EFFECTS/*MICROBIOLOGY NF-kappa B/METABOLISM
Tetradecanoylphorbol Acetate/PHARMACOLOGY Transfection Up-Regulation
(Physiology) Virus Replication/DRUG EFFECTS/PHYSIOLOGY MEETING
ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).