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


CONCLUSIONS
Ceramide induced apoptosis in RA synovial cells. Ceramide could be a second messenger specific for apoptosis of RA synovial cells.
Mizushima
N
N
First Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, Japan.
Kohsaka
H
H
Miyasaka
N
N
D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013583:Synovial Membrane / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D016207:Cytokines; D007375:Interleukin-1; C064769:N-acetylsphingosine; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D004247:DNA; D013110:Sphingosine