FAS AND FAS-MEDIATED EFFECTS ON A HUMAN SALIVARY CELL-LINE IN-VITRO -A MODEL FOR IMMUNE-MEDIATED EXOCRINE DAMAGE IN SJOGRENS-SYNDROME

Sjogren's syndrome (SS) is an autoimmune exocrinopathy characterized b y mononuclear cell infiltration and loss of parenchymal tissue in sali vary and lacrimal glands. The mechanisms for these histologic alterati ons are not known. Apoptotic cell death, induced by the ligation of Fa s (APO-1/CD95) with Pas ligand (FasL/CD95L) may be an explanation for the tissue damage seen in SS. Fas and Fast were detected in minor sali vary glands from SS patients and healthy individuals using immunohisto chemical methods. There was increased expression of both Pas and Fast in the patients. The ability of the Fas-FasL pathway to influence epit helial cell growth and survival was demonstrated in vitro using a huma n submandibular cell line. The presence of Fas receptor was demonstrat ed on the cells. Anti-Pas antibody triggered cell death. Cells were al so grown in the presence of gamma-interferon (IFN-gamma). IFN-gamma in duced an upregulation of Pas receptor expression and pre-treatment of cells with IFN-gamma led to enhanced anti-Pas mediated cell death.