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Tenidap reduces the level of interleukin 1 receptors and collagenase expression in human arthritic synovial fibroblasts


, : Tenidap reduces the level of interleukin 1 receptors and collagenase expression in human arthritic synovial fibroblasts. Journal of Rheumatology 23(1): 24-31

Objective: To investigate the effects of tenidap, a new antirheumatic drug, sodium diclofenac, a nonsteroidal antiinflammatory drug, and a disease modifying antirheumatic drug, hydroxychloroquine, on the level and expression of interleukin 1 receptors (IL-IR) on synovial fibroblasts from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, the effect of tenidap on IL-1 stimulated collagenase gene expression was studied. Methods: Binding assays were performed using (125I)-IL-1-beta as radioligand. Flow cytometry was done using a specific antibody against type I IL-1R. Protein synthesis was determined by (3H)leucine incorporation. Levels of expression were determined by Northern Blot for collagenase and by reverse transcription polymerase chain reaction (RT-PCR) for type I IL-1R. Results: Tenidap produced for both OA and RA synovial fibroblasts a dose dependent decrease in the number of IL-1 binding sites/cell. A reduction of 41% (2.5 mu-g/ml) to 81% (at therapeutic concentration, 20 mu-g/ml) was noted for OA, while 29% (2.5 mu-g/ml) to 89% (20 mu-g/ml) was found for RA cells. Diclofenac produced no effect on OA cells, and minimal inhibition of RA synovial fibroblasts was observed only at pharmacological concentration (12%, 300 mg/ml). Hydroxychloroquine had effects similar to diclofenac. The decreased number of IL-1 binding sites/cell by tenidap was time dependent and reached 93% inhibition after 48 h. The effect of tenidap appears to be posttranscriptional, judged by the marked reduction of the type I IL-1R protein/cell and the absence of effect on its mRNA level. Tenidap also markedly reduced the IL-1 induced collagenase expression in synovial fibroblasts. Conclusion: At therapeutic concentrations tenidap is a potent inhibitor of type I IL-1R in OA and RA synovial fibroblasts. The effect of tenidap was considerably more marked than diclofenac or hydroxychloroquine.

US$29.90

PMID: 8838504


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