BACKGROUND: Cytokines, in particular IL-1, are believed to be responsible for mediating cartilage degradation in osteoarthritis (OA). To investigate the role of the IL-1 system in this disease, we studied in normal and OA human synovial fibroblasts the nature, the number, and the level of expression of the IL-1 receptor (IL-1R) and through which receptor the biologic stimulation of these cells by IL-1 is mediated. EXPERIMENTAL DESIGN: We determined the IL-1R level by radioligand assay, the type of IL-1R with the use of specific antibodies and by the reverse transcriptase-PCR (RT-PCR), and the mRNA level of the type I IL-1R by slot blot analysis. Biologic activity was measured on the synovial fibroblasts via IL-1 binding and prostaglandin E2 production. RESULTS: Binding data revealed the presence of a single class of high affinity IL-1R in both normal (kD, 21 +/- 4.5 pM) and OA (kD, 23 +/- 5.0 pM) human synovial fibroblasts. The number of receptors was significantly higher (p < 0.004) in OA synovial fibroblasts (2534 +/- 187 sites/cell) than in normal cells (1310 +/- 96 sites/cell). This increase was transient; OA synovial fibroblasts in second and third passages had a normal level of IL-1R. Analysis of the mRNA species by RT-PCR revealed that both type I and type II IL-1R are coexpressed in normal and OA synovial fibroblasts; the type I mRNA was the most predominant in all samples. No difference in the relative amount of type I IL-1R mRNA level was found between normal and OA cells. A blocking Ab against the type I IL-1R completely inhibited, in both normal and OA cells, the receptor binding and IL-1 beta stimulated PGE2 production, whereas the treatment with anti-type II IL-1R was ineffective. CONCLUSIONS: These results indicate that the type I IL-1R is up-regulated in OA synovial fibroblasts and is responsible for mediating the biologic activation of these cells by IL-1. This phenomenon is probably secondary to an abnormality in the post-transcriptional regulation of the type I IL-1R. Although type II IL-1R is also expressed, its translation seems to be inoperative, or this receptor is already shed.
BACKGROUND: Cytokines, in particular IL-1, are believed to be responsible for mediating cartilage degradation in osteoarthritis (OA). To investigate the role of the IL-1 system in this disease, we studied in normal and OA human synovial fibroblasts the nature, the number, and the level of expression of the IL-1 receptor (IL-1R) and through which receptor the biologic stimulation of these cells by IL-1 is mediated. EXPERIMENTAL DESIGN: We determined the IL-1R level by radioligand assay, the type of IL-1R with the use of specific antibodies and by the reverse transcriptase-PCR (RT-PCR), and the mRNA level of the type I IL-1R by slot blot analysis. Biologic activity was measured on the synovial fibroblasts via IL-1 binding and prostaglandin E2 production. RESULTS: Binding data revealed the presence of a single class of high affinity IL-1R in both normal (kD, 21 +/- 4.5 pM) and OA (kD, 23 +/- 5.0 pM) human synovial fibroblasts. The number of receptors was significantly higher (p < 0.004) in OA synovial fibroblasts (2534 +/- 187 sites/cell) than in normal cells (1310 +/- 96 sites/cell). This increase was transient; OA synovial fibroblasts in second and third passages had a normal level of IL-1R. Analysis of the mRNA species by RT-PCR revealed that both type I and type II IL-1R are coexpressed in normal and OA synovial fibroblasts; the type I mRNA was the most predominant in all samples. No difference in the relative amount of type I IL-1R mRNA level was found between normal and OA cells. A blocking Ab against the type I IL-1R completely inhibited, in both normal and OA cells, the receptor binding and IL-1 beta stimulated PGE2 production, whereas the treatment with anti-type II IL-1R was ineffective. CONCLUSIONS: These results indicate that the type I IL-1R is up-regulated in OA synovial fibroblasts and is responsible for mediating the biologic activation of these cells by IL-1. This phenomenon is probably secondary to an abnormality in the post-transcriptional regulation of the type I IL-1R. Although type II IL-1R is also expressed, its translation seems to be inoperative, or this receptor is already shed.
Authors: J Fernandes; G Tardif; J Martel-Pelletier; V Lascau-Coman; M Dupuis; F Moldovan; M Sheppard; B R Krishnan; J P Pelletier Journal: Am J Pathol Date: 1999-04 Impact factor: 4.307
Authors: R F Leal; C S R Coy; M L S Ayrizono; J J Fagundes; M Milanski; M J Saad; L A Velloso; J R N Góes Journal: Tech Coloproctol Date: 2008-05-30 Impact factor: 3.781