Proteasome blockers inhibit TNF-alpha release by lipopolysaccharide stimulated macrophages and microglia: implications for HIV-1 dementia.
J Neuroimmunol
; 95(1-2): 55-64, 1999 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-10229115
ABSTRACT
HIV-1 infection of the central nervous system can cause severe neurologic disease although only microglial cells and brain macrophages are susceptible to productive viral infection. Substances secreted by infected cells are thought to cause disease indirectly. Tumor necrosis factor alpha (TNF-alpha) is one candidate neurotoxin and is upregulated during HIV-1 infection of the brain, likely via activation of the transcription factor NF-kappaB. We used the proteasome inhibitors, MG132 and ALLN (N-acetyl-Leu-Leu-Norleucinal), to inhibit NF-kappaB activation in primary human fetal microglia (PHFM) and primary monocyte derived-macrophages, and showed that they could block TNF-alpha release stimulated by lipopolysaccharide (LPS) or TNF-alpha. In addition, we performed electrophoretic mobility shift analysis and determined that in microglia, the p50/p65 heterodimer of NF-kappaB is activated by LPS stimulation, and is inhibited by MG132. Thus, blockade of NF-kappaB activation in microglia in vitro can decrease production of TNF-alpha and may prove to be a novel strategy for treating HIV-1 dementia.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cisteína Endopeptidases
/
Complexo AIDS Demência
/
HIV-1
/
Fator de Necrose Tumoral alfa
/
Microglia
/
Macrófagos
/
Complexos Multienzimáticos
Limite:
Humans
Idioma:
En
Revista:
J Neuroimmunol
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos