Fas ligand and Fas are expressed constitutively in human astrocytes and the expression increases with IL-1, IL-6, TNF-alpha, or IFN-gamma

Fas ligand (FasL) and Fas are mediators of apoptosis, which are implicated in the peripheral deletion of autoimmune cells, activation-induced T cell d eath, and cytotoxicity mediated by CD8(+) T cells. Fas is also believed to be involved in several central nervous system diseases, but until now, the effector cells expressing Fast in the brain have not been identified. We in vestigated the expression levels of Fas and Fast with the stimulation of cy tokines and the possible effector cells targeting Fas-bearing cells. Our da ta demonstrated that: 1) Fast is expressed constitutively on astrocytes tak en from a fetus or an adult and that its expression increases when these ce lls are treated with IL-1, IL-6, or TNF-alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more Fast; 2) astrocytes induce ap optosis in MOLT4 cells through Fast; 3) Fas is also expressed constitutivel y and is upregulated by IL-1, IL-6, or TNP-alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more Fas; 4) apoptosis occurs w hen fetal astrocytes are treated with agonistic: anti-Fas IgM Ab after cult ure with IFN-gamma and TNF-alpha; and 5) TNF-related apoptosis inducing lig and is up-regulated in fetal astrocytes with stimuli of IL-1 or TNF-alpha. These findings suggest a possible role of astrocytes in the induction of ap optosis in central nervous system diseases.