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

Date Published:
08/2003

Publication Type:
Journal Article

Authors:

Secondary:
Journal of Neuroimmunology

Volume:
141

Pagination:
141-9

Issue:
1-2

URL:
https://pubmed.ncbi.nlm.nih.gov/

Keywords:
Antigens;CD95;Cells;Cultured;External;Fas Ligand Protein;Interleukin-1;Ligands;Membrane Glycoproteins;Peptides;Signal Transduction

Abstract:
<p>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.</p>