Hyperplasia of the rheumatoid synovium may result from impaired apoptosis of synovial cells. FLICE-inhibitory protein (FLIP) exerts an anti-apoptotic function by inhibiting Fas mediated apoptosis. The purpose of this study was to determine if FLICE could be detected in synovial tissue samples from patients with rheumatoid arthritis (RA), osteoarthritis (OA). Two normal samples were tested as well.

Results: By reverse transcriptase-PCR, FLIP mRNA was detected in all of the RA and OA synovial fibroblasts, although the expression was very weak in 3 of the 4 OA samples tested. Using in situ hybridization on paraffin embedded synovial sections, FLIP was detected strongly in the lining and sublining layer of the RA synovial tissue samples (8/8), while scattered predominantly in the sublining of one OA sample (1/2). Worth noting is that FLIP was identified at sites demonstrating signs of cartilage and bone destruction. FLIP was not detected in the normal tissue samples (2/2).

Editorial Comment: Synovial hyperplasia in RA was originally assumed to be due to increased proliferation of synovial cells, but studies have repeatedly failed to show increased mitotic activity in RA compared to normal synovium. More recently, it has been hypothesized that hyperplasia is due to prolongation of lifespan of synovial cells through anti-apoptotic mechanisms. FLIP contains a caspase-like domain and prevents the association of caspases 8 and 10 from associating with FAS-associated death domain, and thus exerts an anti-apoptotic function through inhibition of Fas mediated apoptosis. The current studies provide circumstantial evidence that the FLIP protein may play a role in mediating prolonged survival of monocyte and fibroblast derived synovial cells. An increased sample size is needed to validate these findings.

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