CHARACTERIZATION OF SV40T ANTIGEN IMMORTALIZED HUMAN SYNOVIAL FIBROBLASTS - MAINTAINED EXPRESSION PATTERNS OF EGR-1, HLA-DR AND SOME SURFACE-RECEPTORS

In rheumatoid arthritis (RA) synovial fibroblasts are activated by gro wth factors and cytokines to proliferate and to express matrix-degradi ng proteases and pro-inflammatory cytokines. This contributes to carti lage degradation and joint destruction. To analyse the parameters that lead to activation of synovial fibroblasts, we established a stable h uman synoviocyte line (K4IM) from a healthy donor by immortalization w ith SV40 T antigen (TAg). Characterizing the phenotype of the immortal ized K4IM cells, we found that they maintained CD44, CD54 (intercellul ar adhesion molecule; ICAM-1) and CD95 (Fas) expression, but lost the expression of CD106 (vascular cell adhesion molecule 1, VCAM-1) and th e receptors for interleukin 1 (IL-1) and platelet-derived growth facto r (PDGF). We also monitored normal expression kinetics of transcriptio n factor Egr-1 upon activation with tumor necrosis factor alpha (TNF-a lpha) or synovial fluid from RA patients. In addition, we showed that HLA-DR expression could still be upregulated by recombinant interferon gamma (rINF-gamma). The immortalized K4IM cell line therefore represe nts a valuable and unique tool to study mechanisms that induce or main tain synoviocyte activation.