tailieunhanh - Báo cáo y học: "A crucial role for tumor necrosis factor receptor 1 in synovial lining cells and the reticuloendothelial system in mediating experimental arthritis"

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: A crucial role for tumor necrosis factor receptor 1 in synovial lining cells and the reticuloendothelial system in mediating experimental arthritis. | Arntz et al. Arthritis Research Therapy 2010 12 R61 http content 12 2 R61 RESEARCH ARTICLE Open Access A crucial role for tumor necrosis factor receptor 1 in synovial lining cells and the reticuloendothelial system in mediating experimental arthritis Onno J Arntz Jeroen Geurts Sharon Veenbergen Miranda B Bennink Ben Tvan den Brand Shahla Abdollahi-Roodsaz Wim B van den Berg and Fons A van de Loo Abstract Introduction Rheumatoid arthritis RA is an autoimmune inflammatory disease that mainly affects synovial joints. Biologics directed against tumor-necrosis-factor TNF -a are efficacious in the treatment of RA. However the role of TNF receptor-1 TNFR1 in mediating the TNFa effects in RA has not been elucidated and conflicting data exist in experimental arthritis models. The objective is to investigate the role of TNFR1 in the synovial lining cells SLC and the reticuloendothelial system RES during experimental arthritis. Methods Third generation of adenovirus serotype 5 were either injected locally in the knee joint cavity or systemically by intravenous injection into the retro-orbital venous sinus to specifically target SLC and RES respectively. Transduction of organs was detected by immunohistochemistry of the eGFP transgene. An adenoviral vector containing a short hairpin sh RNA directed against TNFR1 HpTNFRI was constructed and functionally evaluated in vitro using a nuclear factor-kappaB NF-kB reporter assay and in vivo in streptococcal cell wall-induced arthritis SCW and collagen-induced arthritis CIA . Adenoviruses were administered before onset of CIA and the effect of TNFR1 targeting on the clinical development of arthritis histology quantitative polymerase chain reaction qPCR cytokine analyses and T-cell assays was evaluated. Results Systemic delivery of predominantly transduced the RES in liver and spleen. Local delivery transduced the synovium and not the RES in liver spleen and draining lymph nodes. In vitro HpTNFR1 .