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).