Abstract
Although fosfomycin (FOM) is known to be a unique antibiotic that has an immunosuppuressive function, the effects of FOM on autoimmune diseases remain unclear. In this study, we report a novel role of FOM in the tissue destruction of an organ-specific autoimmune disease in a murine model of Sjögren's syndrome (SS). When we administered FOM to a murine model of autoimmune exocrinopathy in SS from 4 weeks to 8 or 12 weeks of age, fewer autoimmune lesions were found in the salivary and lacrimal glands of the mice at 12 weeks than in the control mice. In addition, a decreased proportion of TUNEL+ apoptotic epithelial duct cells was observed in the mice given FOM from 4 weeks to 8 weeks. We also found that preincubation with low concentrations of FOM (0.001μg/mL-1.0μg/mL) inhibits anti-Fas-induced apoptosis in human salivary gland cell lines (HSG and HSY). We detected an inhibitory effect of FOM on proteolysis of α-fodrin in HSG and HSY cells with Fas-mediated apoptosis. Furthermore, treatment with FOM suppressed caspase activities (ICE and CPP-32) in salivary gland cells stimulated with anti-Fas mAb. These results suggest that FOM has a theraputic effect on Sjögren's syndrome by inhibiting apoptosis in salivary gland cells.
