Human synovial fibroblasts coexpress IL-1 receptor type I and type II mRNA. The increased level of the IL-1 receptor in osteoarthritic cells is related to an increased level of the type I receptor.
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.


METHODS
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.
Sadouk
M B
MB
Osteoarthritis Research Unit, University of Montreal, L.-C. Simard Research Center, Notre-Dame Hospital Montreal, Canada.
Pelletier
J P
JP
Tardif
G
G
Kiansa
K
K
Cloutier
J M
JM
Martel-Pelletier
J
J
D000368:Aged; D001483:Base Sequence; D002478:Cells, Cultured; D015232:Dinoprostone / Q000032:analysis; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis* / Q000145:classification* / Q000235:genetics; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D015232:Dinoprostone