TY - JOUR
T1 - The Tat protein of HIV-1 induces tumor necrosis factor-α production. Implications for HIV-1-associated neurological diseases
AU - Chen, Peiqin
AU - Mayne, Michael
AU - Power, Christopher
AU - Nath, Avindra
PY - 1997/9/5
Y1 - 1997/9/5
N2 - 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)-α, 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-α. Tat induced TNF-α mRNA and protein production dose- dependently, primarily in macrophages but also in astrocytic cells. The TNF- α induction was NF-κB-dependent and could be eliminated by inhibiting protein kinase A or protein tyrosine kinase activity. In addition, Tat- induced TNF-α 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.
AB - 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)-α, 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-α. Tat induced TNF-α mRNA and protein production dose- dependently, primarily in macrophages but also in astrocytic cells. The TNF- α induction was NF-κB-dependent and could be eliminated by inhibiting protein kinase A or protein tyrosine kinase activity. In addition, Tat- induced TNF-α 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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U2 - 10.1074/jbc.272.36.22385
DO - 10.1074/jbc.272.36.22385
M3 - Article
C2 - 9278385
AN - SCOPUS:0030884230
SN - 0021-9258
VL - 272
SP - 22385
EP - 22388
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 36
ER -