tailieunhanh - Báo cáo y học: " Inhibitor of IκB kinase activity, BAY 11-7082, interferes with interferon regulatory factor 7 nuclear translocation and type I interferon production by plasmacytoid dendritic cells"

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: Inhibitor of IκB kinase activity, BAY 11-7082, interferes with interferon regulatory factor 7 nuclear translocation and type I interferon production by plasmacytoid dendritic cells. | Miyamoto et al. Arthritis Research Therapy 2010 12 R87 http content 12 3 R87 RESEARCH ARTICLE Open Access Inhibitor of IkB kinase activity BAY 11-7082 interferes with interferon regulatory factor 7 nuclear translocation and type I interferon production by plasmacytoid dendritic cells Rie Miyamoto 1 Tomoki Ito 1 Shosaku Nomura1 Ryuichi Amakawa1 Hideki Amuro1 Yuichi Katashiba1 Makoto Ogata1 Naoko Murakami1 Keiko Shimamoto1 Chihiro Yamazaki2 3 Katsuaki Hoshino2 Tsuneyasu Kaisho2 3 4 and Shirou Fukuhara1 Abstract Introduction Plasmacytoid dendritic cells pDCs play not only a central role in the antiviral immune response in innate host defense but also a pathogenic role in the development of the autoimmune process by their ability to produce robust amounts of type I interferons IFNs through sensing nucleic acids by toll-like receptor TLR 7 and 9. Thus control of dysregulated pDC activation and type I IFN production provide an alternative treatment strategy for autoimmune diseases in which type I IFNs are elevated such as systemic lupus erythematosus SLE . Here we focused on IkB kinase inhibitor BAY 11-7082 BAY11 and investigated its immunomodulatory effects in targeting the IFN response on pDCs. Methods We isolated human blood pDCs by flow cytometry and examined the function of BAY11 on pDCs in response to TLR ligands with regards to pDC activation such as IFN-a production and nuclear translocation of interferon regulatory factor 7 IRF7 in vitro. Additionally we cultured healthy peripheral blood mononuclear cells PBMCs with serum from SLE patients in the presence or absence of BAY11 and then examined the inhibitory function of BAY11 on SLE serum-induced IFN-a production. We also examined its inhibitory effect in vivo using mice pretreated with BAY11 intraperitonealy followed by intravenous injection of TLR7 ligand poly U. Results Here we identified that BAY11 has the ability to inhibit nuclear translocation of IRF7 and IFN-a production in human .

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