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Ann Rheum Dis 1998;57:495-499 ( August )

Extended reports

Ceramide, a mediator of interleukin 1, tumour necrosis factor , as well as Fas receptor signalling, induces apoptosis of rheumatoid arthritis synovial cells Noboru Mizushima, Hitoshi Kohsaka, Nobuyuki Miyasaka

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

OBJECTIVESTo 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.
METHODSSynovial 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.
RESULTSC2-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.
CONCLUSIONCeramide induced apoptosis in RA synovial cells. Ceramide could be a second messenger specific for apoptosis of RA synovial cells.

Keywords: ceramide; apoptosis; rheumatoid arthritis

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© 1998 by Annals of the Rheumatic Diseases

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