CD40-Mediated Fas-Dependent Apoptosis in Cultured Salivary Epithelial Cells Derived from Patients with Sjogren's Syndrome

概要

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Fas-mediated apoptosis is thought to be a major mechanism regulating salivary gland destruction in patients with Sjogren's syndrome (SS). Due to the wide discrepancy in the incidence of apoptosis in SS salivary glands, the role of Fas-mediated apoptosis is not known. We therefore studied the molecular mechanisms of salivary epithelial cell death in cultured primary cells. The expression of Fas and CD40 was significantly higher in IFNγ-stimulated SS salivary epithelial cells than in IFNγ-stimulated normal cells (P<0.05 for both). Although an anti-Fas monoclonal antibody alone could not induce apoptosis in Fas-expressing SS salivary epithelial cells, co-activation of Fas and CD40 on the cell surface efficiently induced apoptosis, as shown by cell morphology and a DNA fragmentation assay. A neutralizing anti-Fas mAb completely blocked apoptosis induced by anti-Fas mAb and anti-CD40 mAb in SS salivary epithelial cells. These results suggest that SS salivary epithelial cell death occurs through a pathway involving Fas, whereas CD40 amplifies the Fas death signal.
金沢医科大学の論文