Extended reports
Ceramide, a mediator of interleukin 1, tumour necrosis factor
, as well as Fas receptor signalling, induces apoptosis of
rheumatoid arthritis synovial cells
First Department of
Internal Medicine, School of Medicine, Tokyo Medical and Dental
University, Tokyo, Japan
Correspondence to: Dr H Kohsaka, First Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Accepted for publication 11 June 1998
OBJECTIVES
To examine
the effects of ceramide, which is a lipid second messenger of cell
surface receptors, including tumour necrosis factor
(TNF
),
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.
© 1998 by Annals of the Rheumatic Diseases
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