Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by a hyperplastic synovial tissue, inflammatory infiltrates, and a progressive destruction of cartilage and bone. FLICE‐inhibitory protein (FLIP) prevents the association of caspase 8 with FADD and thus exerts an antiapoptotic effect through inhibition of Fas‐mediated apoptosis. We undertook this study to examine the expression of FLIP in RA, osteoarthritic (OA), and normal synovial tissues.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We investigated the expression of FLIP (long form) in 5 RA, 2 OA, and 2 normal synovial tissue samples. A 393‐bp fragment was amplified from complementary DNA obtained from cultured RA synovial fibroblasts (RASF) by reverse transcription–polymerase chain reaction (RT‐PCR). Using in situ hybridization, the expression of FLIP messenger RNA (mRNA) in paraffin‐embedded synovial tissue sections was investigated semiquantitatively by analyzing the lining layer, the sublining, and sites of invasion. Immunohistochemistry with anti‐CD68 antibodies was performed on serial tissue sections to further characterize the cell types expressing FLIP. In addition, quantitative expression of FLIP was measured by real‐time PCR.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>RT‐PCR revealed the expression of FLIP mRNA in all RA and OA samples tested. Using in situ hybridization in synovial tissue, FLIP was detected in all 5 RA samples and in 1 of 2 OA samples, but in neither of the 2 normal control samples. In RA, FLIP expression could be found in both the lining and sublining layers; most importantly, it could also be identified at sites of cartilage invasion and bone destruction. Moreover, quantitative PCR analysis showed 50% higher FLIP expression in RASF than in OASF.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The expression of antiapoptotic FLIP in RA synovial tissue and in synovial fibroblasts suggests the idea of a novel pathway in RA that potentially extends the lifespan of cartilage‐ and bone‐degrading synovial cells, thus contributing to the progression of joint destruction.</jats:p></jats:sec>