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M94A3234.TXT
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1994-10-25
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Document 3234
DOCN M94A3234
TI Regulation of the MnSOD gene in HIV infected macrophages.
DT 9412
AU Raoul H; Le Naour R; Mabondzo A; Dormont D; SSA/DSV, CEA, Fontenay aux
Roses, France.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):122 (abstract no. PA0109). Unique
Identifier : AIDSLINE ICA10/94369341
AB OBJECTIVE: Because an imbalance between oxydant and anti-oxydant has
been demonstrated in HIV-1 seropositive individuals, and because TNF
alpha seems to regulate the expression of enzymes of the oxidative
burst, like the MnSOD, we tried to determined: 1) the effect of HIV-1
infection on the MnSOD and TNF alpha genes expression in macrophage
cultures; 2) the level of TNF alpha release in the supernatants of the
same cultures; and 3) if an interaction between TNF alpha release and
MnSOD gene regulation exists. METHODS: Human monocytes were obtained
using the elutriation technique. They were cultured for 7 days, and then
infected or not with 3 macrophage-tropic HIV-1 strains (HIV-1/Bal,
HIV-1/PAR, HIV-1/DAS). A TNF alpha inhibitor was also added in the
culture medium when needed. The culture supernatants were collected
every 3 or 4 days and analysed for virus replication and TNF alpha
detection. The cells were harvested at the same time and the expression
levels of the MnSOD and TNF alpha genes were determined by Northern blot
analysis. RESULTS: An increase of MnSOD gene expression in the infected
macrophages compared to the uninfected one was observed at the time of
HIV-1 replication. This increase is correlated to an over-expression of
the TNF alpha gene, as well as to the detection of TNF alpha in the
culture supernatants. Moreover, the use of a TNF alpha inhibitor cancel
the MnSOD gene transcription in the infected macrophages. CONCLUSION:
Our results indicate that 1) HIV-1 replication in normal human
macrophages induces an up-regulation of gene implicated in the oxidative
burst; 2) the relation between MnSOD and TNF alpha observed in other
cellular system, exist in our model; and 3) an inhibition of the TNF
alpha release might have consequences on other cellular metabolism.
DE Blotting, Northern Cells, Cultured Comparative Study *Gene Expression
Regulation, Enzymologic Human HIV-1/*PHYSIOLOGY
Macrophages/ENZYMOLOGY/*MICROBIOLOGY Monocytes/ENZYMOLOGY/*MICROBIOLOGY
Superoxide Dismutase/*BIOSYNTHESIS/GENETICS Transcription, Genetic
Tumor Necrosis Factor/BIOSYNTHESIS/GENETICS *Virus Replication MEETING
ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).