Regulation of Fas and FasL mRNA expression in human astrocytoma cell lines by cytokines

ABSTRACT

Fas-mediated apoptosis is one of the major mechanisms of programmed cell death. Fas is a transmembrane protein of the nerve growth factor/tumor necrosis factor(TNF-alpha) receptor family which signals apoptotic cell death in susceptible target cells when it reacts with Fas ligand(FasL) or anti-Fas antibody. FasL, which belongs to TNF family, is mainly expressed on the surface of activated T lymphocytes and induces apoptosis of Fas-bearing cell. Astrocytoma is the most common brain tumor, which is usually fatal in its malignant form. Astrocytoma appears to progress without any significant impedance from the immune system, even if intratumoral T cell infiltrations are usually found. In the brain, it has been suggested that astrocytoma cells may potentially deliver a death signal to Fas-bearing cells which include infiltrating leukocytes as well as, paradoxically, astrocytoma cells themselves. In this study, we show that all of the astrocytoma cell lines express both Fas and FasL, which is confirmed by reverse transcription-PCR. Pre-exposure to IFN-gamma, IL-1 and TNF-alpha were found to augment the expression of Fas and FasL. These findings suggest that FasL-induced apoptosis by astrocytoma cells may play a significant role in both the immunosuppression and the regulation of tumor growth within the central nervous system. And also cytokines might play a role in the induction of Fas and FasL in astrocytoma cells.