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1996-02-27
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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).