J Korean Soc Microbiol.
2000 Feb;35(1):9-18.
Interaction of HIV-1 core p24 antigen with human monocytic cell line THP1
results in TNF-alpha dependent secretion of matrix metalloproteinase-9
- Affiliations
-
- 1Department of Microbiology, College of Medicine, Ewha
Womans University, 911-1, Mok-6-dong, Yangcheonku, Seoul, 158-056, South
Korea.
Abstract
-
Immunological mechanisms involving the release of inflammatory
factors by HIV-1 infected microglia in the brain have been implicated in
the pathogenesis of HIV dementia (HIVD). Since the regulation of matrix
metalloproteinases (MMPs) activity can be influenced by variety of
inflammatory mediators, this study was undertaken to look for a
correlation between the MMP-9 release and the production of TNF-alpha in
response to HIV-1 p24 in the human monocyte cell line THP-1 as a model
for microglia. First, it was shown that HIV-1 core p24 antigen induced
THP-1 to secrete MMP-9 in a dose response manner while it elicited a
little effect on MMP-2 release in human astroglial cell line T98G. Next,
it was found that p24 induced THP-1 to secrete TNF-alpha without prior
differentiation into macrophages by phorbol myristate acetate (PMA)
treatment. Furthermore, anti-TNF-alpha neutralizing antibodies
significantly blocked p24-induced MMP-9 release in a dose dependent
manner. Our data indicate that p24 antigen induces monocytic MMP-9
release by triggering up-regulation of TNF-alpha secretion.