The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-κB transcriptional activity in models of rheumatoid arthritis

摘要: Rheumatoid arthritis (RA) is a chronic inflammatory disease that produces synovial proliferation and joint erosions. The pathologic lesions of RA are driven through the production mediators in synovium mediated, part, by transcription factor NF-κB. We have identified non-steroidal estrogen receptor ligand, WAY-169916, selectively inhibits NF-κB transcriptional activity but devoid conventional estrogenic activity. WAY-169916 was monitored two models arthritis, HLA-B27 transgenic rat Lewis adjuvant-induced model, after daily oral administration. In both models, near complete reversal hindpaw scores observed as well marked improvements histological scores. adjuvant markedly suppresses induction three serum acute phase proteins: haptoglobin, α1-acid glycoprotein (α1-AGP), C-reactive protein (CRP). Gene expression experiments also demonstrate global suppression gene spleen, liver, popliteal lymph nodes. Finally, effective suppressing tumor necrosis factor-α-mediated fibroblast-like synoviocytes isolated from patients with RA. Together, these data suggest utility other compounds its class, treating inflammation via selective blockade