HIV-1 and IL-1 beta regulate Fas ligand expression in human astrocytes through the NF-kappa B pathway.
Reactive astrogliosis is a prominent pathological feature of HIV-1-associated dementia (HAD). We hypothesized that in HAD, astrocytes activated with proinflammatory stimuli such as IL-1beta express Fas ligand (FasL), a death protein. IL-1beta and HIV-1-activated astrocytes expressed FasL mRNA and protein. Luciferase reporter constructs showed that IL-1beta and HIV-1 upregulated FasL promoter activity (p<0.001). The NF-kappaB pathway was involved as shown by inhibition with SN50 and dominant negative IkappaBalpha mutants. Brain extracts from HAD patients had significantly elevated FasL levels compared to HIV-seropositive (p<0.001) and seronegative individuals (p<0.01). We propose that astrocyte expression of FasL may participate in neuronal injury in HAD.
Ghorpade
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A
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5215, USA. aghorpad@unmc.edu
Holter
S
S
Borgmann
K
K
Persidsky
R
R
Wu
L
L
D015526:AIDS Dementia Complex / Q000276:immunology; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005333:Fetus; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000134:cerebrospinal fluid / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007375:Interleukin-1; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide; D019014:fas Receptor