tailieunhanh - Báo cáo y học: "The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-κB transcriptional activity in models of rheumatoid arthrits"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-κB transcriptional activity in models of rheumatoid arthritis. | Available online http content 7 3 R427 Research article The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-KB transcriptional activity in models of rheumatoid arthritis James C Keith Jr1 Leo M Albert1 Yelena Leathurby1 Max Follettie2 Lili Wang2 Lisa Borges-Marcucci3 Christopher C Chadwick4 Robert J Steffan5 and Douglas C Harnish3 Cardiovascular and Metabolic Disease Research Wyeth Research Cambridge MA USA 2Department Biological Technologies Cambridge MA USA 3Cardiovascular and Metabolic Disease Research Collegeville PA USA 4Women s Health Research Institute Collegeville PA USA 5Chemical and Screening Sciences Collegeville PA USA Corresponding author Douglas C Harnish harnisd@ Received 3 Jun 2004 Revisions requested 29 Jun 2004 Revisions received 12 Jan 2005 Accepted 1 7 Jan 2005 Published 21 Feb 2005 Arthritis Research Therapy 2005 7 R427-R438 DOI ar1692 2005 Keith et al. licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Open Access Abstract 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 of inflammatory mediators in the synovium mediated in part by the transcription factor NF-kB. We have identified a non-steroidal estrogen receptor ligand WAY-169916 that selectively inhibits NF-kB transcriptional activity but is devoid of conventional estrogenic activity. The activity of WAY-169916 was monitored in two models of arthritis the HLA-B27 transgenic rat and the Lewis rat adjuvant-induced model after daily oral administration. In both models a near complete reversal in hindpaw scores was observed as well as marked improvements