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
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