HIV-1 and IL-1β regulate Fas ligand expression in human astrocytes through the NF-κB 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-1β express Fas ligand (FasL), a death protein. IL-1β and HIV-1-activated astrocytes expressed FasL mRNA and protein. Luciferase reporter constructs showed that IL-1β and HIV-1 upregulated FasL promoter activity (p<0.001). The NF-κB pathway was involved as shown by inhibition with SN50 and dominant negative IκBα 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.