Fas antigen expression on synovial cells was down-regulated by interleukin 1 beta.
Recent reports revealed that Fas antigen is functionally expressed on human synovial cells and apoptosis can be induced in these cells by anti-Fas antibody. We examined the effect of interleukin 1 beta (IL-1 beta) on Fas antigen-mediated apoptosis on human synovial cells in vitro. Using flowcytometric analysis, IL-1 beta inhibited Fas antigen expression on synovial cells in a dose-dependent fashion. No significant difference of Fas antigen gene expression between IL-1 beta-treated and untreated synovial cells was observed by RT-PCR analysis, suggesting that the inhibitory effect of Fas antigen expression by IL-1 beta is at posttranscriptional level. Apoptosis of synovial cells was easily induced by treatment of these cells with anti-Fas antibody. In contrast, pretreatment of synovial cells with IL-1 beta protected these cells against Fas antigen-mediated apoptosis. The expression of bcl-2 on synovial cells, known to interfere with the apoptotic process mediated by the Fas antigen, was not influenced by IL-1 beta. Our results suggest that IL-1 beta inhibits Fas antigen-mediated apoptosis of synovial cells and may perpetuate the hyperplasia of the synovium in patients with rheumatoid arthritis.
Tsuboi
M
M
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Kawakami
A
A
Matsuoka
N
N
Kawabe
Y
Y
Aoyagi
T
T
Maeda
K
K
Nagataki
S
S
D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis*
D017931:DNA Primers; D007375:Interleukin-1; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D019014:fas Receptor