Preferential expression of tumor necrosis factor receptor 55 (TNF-R55) on human articular chondrocytes: Selective transcriptional upregulation of TNF-R75 by proinflammatory cytokines interleukin 1 beta, tumor necrosis factor-alpha, and basic fibroblast growth factor

Objective. Articular cartilage is the main target for tumor necrosis factor -alpha (TNF-alpha) and interleukin 1 (IL-1) actions. These cytokines are be lieved to mediate cartilage degradation in arthritis. We studied the expres sion of TNF receptors (TNF-R) on human articular chondrocytes and their reg ulation by IL-1 beta, TNF-alpha, and basic fibroblast growth factor (bFGF). Methods. The expression of TNF-R55 and TNF-R75 on human nonarthritic articu lar chondrocytes was analyzed on protein and mRNA levels by ligand binding studies and reverse transcription polymerase chain reaction (RT-PCR) techni que. The regulation of these receptors induced by IL-1 beta, TNF-alpha, and bFGF on mRNA level was studied using RT-PCR. Results. Both TNF-R55 and TNF-R75 are expressed constitutively on human art icular chondrocytes, and the number of both receptors varied between 822 an d 3880 receptors per cell, depending on the donor cartilage used. Using TNF receptor-specific antibodies, we show that normal chondrocytes express mai nly TNF-R55. These results are consistent with the mRNA data obtained by RT -PCR. mRNA expression of TNF receptors is regulated by IL-1 beta, TNF-alpha , and bEGF. On human chondrocytes the expression of TNF-R75 mRNA was marked ly upregulated by IL-1 beta, TNF-alpha, and bFGF, whereas the expression of TNF-R55 mRNA remained largely unchanged. A combination of IL-1 beta and TN F-alpha, but not of IL-1 beta and bFGF, showed an additive effect on TNF-R7 5 mRNA expression. Conclusion. The expression of TNF-R55 and TNF-R75 on human articular chondr ocytes is modulated independently by IL-1 beta, TNF-alpha, and bFGF, sugges ting a role of these regulatory mechanisms in the degradation processes of human articular cartilage in inflammatory joint diseases.