HIV-1 and IL-1 beta regulate Fas ligand expression in human astrocytes through the NF-kappa B pathway

TitleHIV-1 and IL-1 beta regulate Fas ligand expression in human astrocytes through the NF-kappa B pathway
Publication TypeJournal Article
Year of Publication2003
AuthorsGhorpade, A, Holter, S, Borgmann, K, Persidsky, R, Wu, L
JournalJournal of Neuroimmunology
Volume141
Issue1-2
Pagination141-9
Date Published08/2003
KeywordsAntigens, CD95, Cells, Cultured, External, Fas Ligand Protein, Interleukin-1, Ligands, Membrane Glycoproteins, Peptides, Signal Transduction
Abstract

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.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/12965265