You Position: Home > Paper
Mechanism for cytoplasmic transduction peptideHBcAg18-27-Tapasin to induce HBV specific CTL response in C57BL/6 mice
( views:11, downloads:0 )
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 17
- DOI:
- 10.11569/wcjd.v24.i17.2688
- Key Word:
- CTP-HBcAg18-27-Tapasin;HBV特异性CTL反应;JAK/STAT信号通路;Cytoplasmic transduction peptideHBcAg18-27-Tapasin;HBV-specific cytotoxic T lymphocyte response;JAK/STAT signal pathway
Abstract： 目的:观察融合蛋白胞质转导肽(cytoplasmic transduction peptide,CTP)-HBcAg18-27-Tapasin通过介导JAK/STAT通路诱导近交系C57BL/6小鼠HBV特异性细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)反应.方法:C57BL/6小鼠随机分为4组:CTP-HBcAg18-27-Tapasin实验组、CTP-HBcAg18-27-Tapasin+AG490对照组、AG490对照组、PBS空白组.融合蛋白经肌肉注射免疫小鼠,腹腔注射AG490阻断JAK/STAT通路,CCK-8比色法检测T淋巴细胞增殖活性;流式细胞术检测T淋巴细胞内的的细胞因子;ELISA检测T淋巴细胞分泌细胞因子,Real-time PCR检测JAK/STAT通路信号分子表达水平.结果:CTP-HBcAg18-27-Tapasin组相比CTP-HBcAg18-27-Tapasin+AG490组CD8+IFN-y+T双阳性细胞百分比显著增加(P＜0.01),淋巴细胞增殖活性差异具有显著性(P＜0.01),Th1型细胞因子分泌水平显著增加(P＜0.01),其他各组之间没有显著性差异,JAK/STAT信号通路信号中Jak2,STAT4 mRNA分子表达水平CTP-HBcAg18-27-Tapasin组相比其他对照组表达水平差异具有显著性(P＜0.05),CTP-HBcAg18-27-Tapasin组Tyk2、STAT1mRNA的分子表达水平相比其他对照组表达水平具有显著性差异(P＜0.01).结论:本研究表明CTP-HBcAg18-27-Tapasin通过JAK/STAT信号通路促进Th1型细胞因子的分泌而促进特异性CTL反应.
- [1]唐余燕,陈小华,周丽芹,等.胞质转导肽-HBcAg18-27-Tapasin诱导特异性细胞毒性T淋巴细胞抑制转基因小鼠HBV复制[J].2014,(1).
- [2]刘红红,陈小华,周丽芹,等.CTP-HBcAg18-27-Tapasin融合表达载体的构建及其表达和纯化[J].2013,(7).
- [3]R G, Paul,S T, Roodman,C R, Campbell,etc.HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B.[J].1991,13(5).
- [4]Puja, Khanna,Pei Jou, Chua,Boon Huat, Bay,etc.The JAK/STAT signaling cascade in gastric carcinoma (Review).[J].2015,47.
- [5]Yukihiro Shimizu.T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis B virus infection[J].2012,(20).
- [6]Boni C,Fisicaro P,Valdatta C,etc.Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection[J].2007,81(8).
- [7]Boyle, Louise H.,Antoniou, Antony N.,Hein, Zeynep,etc.F pocket flexibility influences the tapasin dependence of two differentially disease-associated MHC Class I proteins[J].2015,45(4).
- [8]F V, Chisari,C, Ferrari.Hepatitis B virus immunopathogenesis.[J].1995,13.
- [9]Rehermann B.Immune responses in hepatitis B virus infection.[J].2003,23(1).
- [10]Valeriya Gyurkovska,Nina Ivanovska.Tyrosine kinase inhibitor tyrphostin AG490 reduces liver injury in LPS-induced shock[J].2015,751.
- [11]Levrero, Massimo,Zucman-Rossi, Jessica.Mechanisms of HBV-induced hepatocellular carcinoma[J].2016,64(1S).
- [12]Han, Seung-Soo,Lee, Jinjoo,Jung, Yideul,etc.Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system[J].2015,33(38).
- [13].A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes[J].2014,5(4).
- [14]Chen,X.,Tang,Y.,Zhang,Y.,etc.Tapasin modification on the intracellular epitope HBcAg 18-27 enhances HBV-specific CTL immune response and inhibits hepatitis B virus replication in vivo[J].2014,94(5).
- [15]Chung JS,Isogawa M,Chisari FV,etc.Immunogenicity and tolerogenicity of hepatitis B virus structural and nonstructural proteins: Implications for immunotherapy of persistent viral infections[J].2002,76(17).
- [16]Stark,G.,Darnell,J..The JAK-STAT Pathway at Twenty[J].2012,36(4).
- [17].Regulation of Jak--Stat Signalling in the Immune System.[J].2003,3(11).
- [18]Pape GR,Jung MC.Immunology of hepatitis B infection.[J].2002,2(1).
- [19]Chitnis T,Sayegh MH,Khoury SJ,etc.Defining Th1 and th2 immune responses in a reciprocal cytokine environment in vivo.[J].2004,172(7).
- [20]Shiratori Y,Hakoda T,Shimada N,etc.HBcAg-specific CD8 T cells play an important role in virus suppression, and acute flare-up is associated with the expansion of activated memory T cells.[J].2003,23(3).
- [21]Kaplan MH,Zhang S,Chang HC.Neonatal tolerance in the absence of stat4- and stat6- dependent th cell differentiation.[J].2002,169(8).
- [22]Kiu,H.,Nicholson,S.E..Biology and significance of the JAK/STAT signalling pathways[J].2012,30(2).
- [23]Lai, Jinglan,Pan, Qingchun,Zang, Guoqing,etc.The delivery of HBcAg via Tat-PTD enhances specific immune response and inhibits Hepatitis B virus replication in transgenic mice[J].2010,28(23).