       Document 0346
 DOCN  M9630346
 TI    Interferon-gamma inhibits HIV-induced invasiveness of monocytes.
 DT    9603
 AU    Dhawan S; Wahl LM; Heredia A; Zhang Y; Epstein JS; Meltzer MS; Hewlett
       IK; Division of Transfusion Transmitted Diseases, Center for; Biologics
       Evaluation and Research, Food and Drug Administration,; Rockville,
       Maryland 20852-1448, USA.
 SO    J Leukoc Biol. 1995 Dec;58(6):713-6. Unique Identifier : AIDSLINE
       MED/96107365
 AB    HIV-infected monocytes form highly invasive network on basement membrane
       matrix and secrete high levels of 92-kd metalloproteinase (MMP-9), an
       enzyme that degrades basement membrane proteins. In the present study,
       using matrigel as a model basement membrane system, we demonstrate that
       treatment of human immunodeficiency virus (HIV)-infected monocytes with
       interferon-gamma at 50 U/ml inhibited the ability of infected monocytes
       to form an invasive network on matrigel and their invasion through the
       matrigel matrix. These effects were associated with a significant
       reduction in the levels of MMP-9 produced by HIV-infected monocytes
       treated with interferon-gamma 1 day prior to infection with HIV as
       compared with that of untreated HIV-infected monocytes. Monocytes
       treated with interferon-gamma 1 day after HIV infection showed the
       presence of integrated HIV sequences; however, the levels of MMP-9 were
       substantially lower than those produced by monocytes inoculated with
       live HIV, heat-inactivated HIV, or even the control uninfected
       monocytes. Exposure of monocytes to heat-inactivated HIV did not result
       in increased invasiveness or high MMP-9 production, suggesting that
       regulation of metalloproteinase by monocytes was independent of
       CD4-gp120 interactions and required active virus infection. Furthermore,
       addition of interferon-gamma to monocytes on day 10 after infection
       inhibited MMP-9 production by more than threefold with no significant
       reduction of virus replication. These results indicate that the
       mechanism of interferon-gamma-induced down-regulation of MMP-9 levels
       and reduced monocyte invasiveness may be mediated by a mechanism
       independent of antiviral activity of IFN-gamma in monocytes.
       Down-regulation of MMP-9 in HIV-infected monocytes by interferon-gamma
       may play an important role in the control of HIV pathogenesis.
 DE    Antiviral Agents/*PHARMACOLOGY  Basement Membrane/PATHOLOGY  Cells,
       Cultured  Collagenases/BIOSYNTHESIS  Human  HIV/*DRUG
       EFFECTS/PATHOGENICITY  Interferon Type II/*PHARMACOLOGY  Monocytes/*DRUG
       EFFECTS/PATHOLOGY/VIROLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

