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(Received for publication, May 29, 1997, and in revised form, July 3, 1997)
From the Department of Human immunodeficiency virus (HIV) infection may
cause a dementing illness. HIV-mediated dementia is clinically and
pathologically correlated with the infiltration of activated
macrophages and elevated levels of tumor necrosis factor (TNF)-
Volume 272, Number 36,
Issue of September 5, 1997
pp. 22385-22388
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
COMMUNICATION:
Production
IMPLICATIONS FOR HIV-1-ASSOCIATED NEUROLOGICAL DISEASES
,
,¶
and¶
Medical Microbiology and
Section of Neurology, ¶ Department of Medicine, University of
Manitoba, Winnipeg, Manitoba, Canada R3E 0W3
,
both of which occur in an environment of small numbers of infected
cells. We examined the possibility that HIV protein Tat, which is
released extracellularly from infected cells, may induce the production of TNF-. Tat induced TNF- mRNA and protein production
dose-dependently, primarily in macrophages but also in
astrocytic cells. The TNF- induction was
NF-
B-dependent and could be eliminated by inhibiting protein kinase A or protein tyrosine kinase activity. In addition, Tat-induced TNF- release was also linked to phospholipase C
activation. However, Tat effects were independent of protein kinase C. These observations suggest that Tat may provide an important link
between HIV and macrophage/glial cell activation and suggest new
therapeutic approaches for HIV dementia.
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