Induction of salivary gland epithelial cell injury in sjogren's syndrome: In vitro assessment of T cell-derived cytokines and fas protein expression

Sjogren's syndrome (SS) is an exocrinopathy characterized by T cell infiltr ates, salivary gland epithelial cell (SGEC) apoptosis and high Fas and FasL expression. To address the participation of T cell-derived cytokines and o f Fas apoptotic pathway in SS glandular lesions, we utilized non-neoplastic SGEC lines established from SS patients and controls. Possibly attesting t o their intrinsic activation, cell lines derived from SS patients displayed significantly higher constitutive Fas and FasL than controls. Surface co-e xpression of Fas and FasL was not associated with spontaneous fratricide ap optosis. SGEC were resistant to anti-Fas-mediated apoptosis (possibly owing to the constitutive expression of anti-apoptotic proteins cFLIP and Bcl-2) , but became sensitive after protein or RNA synthesis inhibition. IFN-gamma and TNF-alpha were able to upregulate surface Fas and FasL, whereas IL-1 b eta downregulated surface FasL. IFN-gamma (but not several other cytokines) reduced the survival of SGEC in a close- and time-dependent manner and ind uced Fas/FasL-mediated apoptosis, directly and via anoikia. Dexamethasone i nhibited the upregulation of Fas and FasL by IFN-gamma and the induction of SGEC apoptosis and detachment by anti-Fas mAb or IFN-gamma. Our findings i ndicate the injurious role of IFN-gamma for the salivary epithelia of SS pa tients through the induction of Fas-mediated apoptosis and anoikia. (C) 200 1 Academic Press.