Ceramide, a mediator of interleukin 1, tumour necrosis factor alpha, as well as Fas receptor signalling, induces apoptosis of rheumatoid arthritis synovial cells

OBJECTIVES: To examine the effects of ceramide, which is a lipid second messenger of cell surface receptors, including tumour necrosis factor alpha (TNF alpha), interleukin 1 (IL1), and Fas receptors, on rheumatoid arthritis (RA) synovial cells. METHODS: Synovial cells from RA patients and normal skin fibroblasts were cultured with cell permeable ceramide (C2-ceramide). Apoptosis was assessed by microscopic observation of morphological changes, nuclear staining, and DNA electrophoresis. DNA synthesis was examined by thymidine incorporation. RESULTS: C2-ceramide induced reversible morphological changes of synovial cells such as cell rounding within four hours. Subsequently, irreversible nuclear changes characteristic to apoptosis were observed at 48 hours. DNA synthesis was not promoted. The addition of ceramide exerted similar effects on cultured dermal fibroblasts. CONCLUSION: Ceramide induced apoptosis in RA synovial cells. Ceramide could be a second messenger specific for apoptosis of RA synovial cells.