Expression of TNF-related apoptosis inducing ligand (TRAIL) on infiltrating cells and of TRAIL receptors on salivary glands in patients with Sjögren's syndrome

Background Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induces apoptosis of tumor cells but not normal cells; its role in normal non-transformed tissues is unknown. Objective To evaluate the role of apoptosis mediated by TRAIL and TRAIL-receptor (TRAIL-R) system in lymphocytic sialadenitis in patients with Sjogren's syndrome. Methods The expression of TRAIL and TRAIL-RI, 2, 3 and 4 in lymphocytic sialadenitis was examined by immunoperoxidase staining in patients with Sjogren's syndrome and in normal subjects. To elucidate the mechanism of de novo expression of TRAIL-RI antigen, we quantitatively investigated its induction by cytokines in human salivary duct cell line (HSG) by cell enzyme-linked immunosorbent assay. In human salivary duct cells stimulated by cytokines, we investigated the induction of apoptotic cell death by recombinant TRAIL protein. Results In patients with massive mononuclear cell infiltration, some infiltrating cells showed TRAIL. In patients with severe lymphocytic sialadenitis, TRAIL-R1, TRAIL-R2, or both were strongly expressed on the ductal epithelial cells. Neither TRAIL-R3 nor R4 were observed on ductal epithelium. In contrast, TRAIL-RI and R2 were not found in the minor salivary glands of normal subjects or patients with mild lymphocytic sialadenitis. Unstimulated HSG cells did not express TRAIL-RI. Interferon-γ (IFN-γ) consistently upregulated levels of TRAIL-R1. In contrast, tumor necrosis factor-a (TNF-a), interleukin 1-β (IL-1β), IL-2, and IL-4 had no effect on TRAIL-R1 levels. HSG cells expressing TRAIL-RI in response to IFN-y were susceptible to apoptosis by recombinant TRAIL protein. Conclusion Our findings suggest that TRAIL and TRAIL-R system may play a role in the pathogenesis of lymphocytic sialadenitis in patients with Sjogren's syndrome.