TREATMENT OF ARTHRITIS WITH ANTISENSE ORIGONUCLEOTIDE FOR TRANSCRIPTION FACTOR NF-κB

点击翻译按钮获取中文摘要

1. DBA/1J male mice were immunized with bovine type II collagen emulsified with Freund's incomplete adjuvant as a model for rheumatoid arthritis. Five mice were sacrificed at 3,5,7 weeks after the immunization. Knee joints were fixed in 10% neutralized formic acid, decalcified with 0.5% EDTA and embedded in paraffin. Histological changes were evaluated in sections stained with hematoxylin-eosin and immunostaining with rabbit anti-NF-κB p65 polyclonal antibodies (Santa Cruz) using avidin-biotin complex method. NF-κB was positive in synovial lining cells and chondrocytes. The mean rates of NF-κB-positive chondrocye at 3,5 and 7 weeks after the immunization were 43.7%, 68.0% and 79.5%. The rate of mice without treatment was 51.1%.2. Antisense oligonucleotide for NF-κB designed as 5'-GAA ACAGATCGTCCATGGT or a mismatched sense designed as 5'-GAAACAGATCGTCTATGGT was intraperitonealy injected into the DBA/1J mice 4 weeks after the immunization with type II collagen for 2 weeks every day. Significant inhibition of swelling and redness of pows was not observed. These findings indicated two critical problems as follows. One was a delivery system of the oligonucleotide, and the other was an effect of another transcription factor AP-1. After then we observed AP-1 expression in the lining cells of mouse air-pouch model induced by lipopolysaccharide. Further investigation on these points will be required.