Inhibitory effects of human immunodeficiency virus gp120 and Tat on CpG-A-induced inflammatory cytokines in plasmacytoid dendritic cells  

作　　者：Meixin Fang Ning Xu Xueting Shao Jin Yang Nanping Wu Hangping Yao 

机构地区：[1]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,Institute of Infectious Diseases,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China [2]College of Pharmaceutical Science,Zhejiang University of Technology,Hangzhou 310018,China

出　　处：《Acta Biochimica et Biophysica Sinica》2012年第9期797-804,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China （30972777） and the National Eleventh Five-Year Plan Key Program of Major Infectious Diseases （2012ZX10001003-002-020） （to H.Y.） of China.

摘　　要：Plasmacytoid dendritic cells （pDCs）, not only inhibit viral replication, but also play an essential role in linking the innate and adaptive immune system. In this study, we explored the effects of human immunodeficiency virus （HIV） gpl20 and tat on CpG-A-induced inflammatory cytokines in pDCs. The results provided fundamental insights into HIV pathogenesis that may hold promise for preventative and even curative strategies, pDCs were isolated using blood DC antigen 4 （BDCA-4） DC isolation kit, and the purity was analyzed using BDCA-2 anti- body by flow cytometry, pDCs and peripheral blood mononuclear cells （PBMCs） were stimulated by either CpG-A （5 μg/mi）, gpl20 （0.5 μg/ml）, tat （0.5 μg/ml）, or CpG-A treatment combined with gp120 or tat. The production of type I interferons （IFNs） and other inflammatory cytokines, including tumor necrosis factor-alpha （TNF-α, interlukine-6 （IL-6）, and interferon-gamma- inducible protein-10 （IP-10） in the culture supernatant,was determined by enzyme-linked immunosorbent assay. The results showed that CpG-A induced high levels of type I IFNs and other inflammatory cytokines, including TNF-α, IL-6, and IP-10, in pDCs. Concomitant treatment with gpl20 reduced the levels of IFN-α, IFN-β, TNF-α, IL-6, and IP-10 induced by CpG-A in pDCs by 79%, 53%, 60%, 50%, and 34%, respectively, while tat suppressed them by 88%, 66%, 71%, 64%, and 53%, respectively. Similar results were demonstrated in CpG- A-treated PBMCs. In conclusion, gpl20 and tat are effective inhibitors of the CpG-A-mediated induction of type I IFNs and other inflammatory cytokines from pDCs and PBMCs.Plasmacytoid dendritic cells （pDCs）, not only inhibit viral replication, but also play an essential role in linking the innate and adaptive immune system. In this study, we explored the effects of human immunodeficiency virus （HIV） gpl20 and tat on CpG-A-induced inflammatory cytokines in pDCs. The results provided fundamental insights into HIV pathogenesis that may hold promise for preventative and even curative strategies, pDCs were isolated using blood DC antigen 4 （BDCA-4） DC isolation kit, and the purity was analyzed using BDCA-2 anti- body by flow cytometry, pDCs and peripheral blood mononuclear cells （PBMCs） were stimulated by either CpG-A （5 μg/mi）, gpl20 （0.5 μg/ml）, tat （0.5 μg/ml）, or CpG-A treatment combined with gp120 or tat. The production of type I interferons （IFNs） and other inflammatory cytokines, including tumor necrosis factor-alpha （TNF-α, interlukine-6 （IL-6）, and interferon-gamma- inducible protein-10 （IP-10） in the culture supernatant,was determined by enzyme-linked immunosorbent assay. The results showed that CpG-A induced high levels of type I IFNs and other inflammatory cytokines, including TNF-α, IL-6, and IP-10, in pDCs. Concomitant treatment with gpl20 reduced the levels of IFN-α, IFN-β, TNF-α, IL-6, and IP-10 induced by CpG-A in pDCs by 79%, 53%, 60%, 50%, and 34%, respectively, while tat suppressed them by 88%, 66%, 71%, 64%, and 53%, respectively. Similar results were demonstrated in CpG- A-treated PBMCs. In conclusion, gpl20 and tat are effective inhibitors of the CpG-A-mediated induction of type I IFNs and other inflammatory cytokines from pDCs and PBMCs.

关 键 词：Type I interferons plasmacytoid dendriticcells CYTOKINES gpl20 tat 

分 类 号：S856.9[农业科学—临床兽医学] Q987[农业科学—兽医学]