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 growth factors and cytokines to proliferate and to express matrix-degrading proteases and pro-inflammatory cytokines. This contributes to cartilage degradation and joint destruction. To analyse the parameters that lead to activation of synovial fibroblasts, we established a stable human synoviocyte line (K4IM) from a healthy donor by immortalization with SV40 T antigen (TAg). Characterizing the phenotype of the immortalized K4IM cells, we found that they maintained CD44, CD54 (intercellular adhesion molecule; ICAM-1) and CD95 (Fas) expression, but lost the expression of CD106 (vascular cell adhesion molecule 1; VCAM-1) and the receptors for interleukin 1 (IL-1) and platelet-derived growth factor (PDGF). We also monitored normal expression kinetics of transcription factor Egr-1 upon activation with tumor necrosis factor alpha (TNF-alpha) 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 represents a valuable and unique tool to study mechanisms that induce or maintain synoviocyte activation.
Haas
C
C
Clinical Research Unit for Rheumatology, University Hospital, Freiburg, Germany.
Aicher
W K
WK
Dinkel
A
A
Peter
H H
HH
Eibel
H
H
D000957:Antigens, Viral, Tumor; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D051766:Early Growth Response Protein 1; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D017874:Immediate-Early Proteins; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D013539:Simian virus 40 / Q000276:immunology*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis*
D000957:Antigens, Viral, Tumor; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D006684:HLA-DR Antigens; D017874:Immediate-Early Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors