Microglial cell upregulation of HIV-1 expression in the chronically infected promonocytic cell line U1: the role of tumor necrosis factor-alpha.
Culture supernatants from lipopolysaccharide (LPS)-treated murine microglial cells were found to markedly induce the expression of human immunodeficiency virus (HIV)-1 in the chronically infected human promonocytic cell line U1 as detected by measurements of HIV-1 p24 antigen release into U1 culture supernatants. Antibody to tumor necrosis factor (TNF)-alpha had an inhibitory effect on the induction of virus by microglial cell supernatants. Also, treatment of microglia with pentoxifylline, an inhibitor of TNF-alpha production, resulted in suppressed amounts of TNF in the supernatants of LPS-treated microglia and in a reduced stimulatory capacity of these supernatants on HIV-1 expression in U1 cells. These findings support the concept that TNF-alpha production by glial cells plays a pathogenetic role in HIV-1-associated brain disease by promoting the expression of the virus in infected cells.
Peterson
P K
PK
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN.
Gekker
G
G
Hu
S
S
Schoolov
Y
Y
Balfour
H H
HH
Chao
C C
CC
D015526:AIDS Dementia Complex / Q000209:etiology* / Q000382:microbiology; D001921:Brain / Q000382:microbiology; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008070:Lipopolysaccharides; D009457:Neuroglia / Q000502:physiology*; D010431:Pentoxifylline / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation
D016655:HIV Core Protein p24; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline