Influence of Notch signaling pathway on interleukin-22 secreted by CD4~+T cells in patients with hepatitis B
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摘要: 目的观察抑制Notch信号通路对乙型肝炎患者CD4+T淋巴细胞分泌白细胞介素(IL)22的影响,初步阐释Notch-IL-22信号通路在乙型肝炎发病中的作用。方法收集2013年7月-2014年12月在唐都医院门诊就诊和住院的乙型肝炎初治患者45例,其中急性乙型肝炎(AHB)13例和慢性乙型肝炎(CHB)32例,另收集20例健康志愿者作为对照组(NC组),分离CD4+T淋巴细胞,应用实时定量PCR法检测Notch1和Notch2 mRNA的表达水平。应用抗CD3抗体或HBV核心区多肽库刺激CD4+T淋巴细胞,同时加入Notch信号通路抑制剂DAPT,应用实时定量PCR法检测培养细胞中IL-22 mRNA的水平,应用ELISA法检测培养上清中IL-22分泌蛋白的水平。采用Kruskal-Wallis H检验对不同组间数据进行统计分析,Dunn’s多重检验对组间数据进行两两比较。结果 Notch1 mRNA在CHB患者CD4+T淋巴细胞中的表达水平约为NC组的2倍(Z=7.708,P=0.018),Not...
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关键词:
- 肝炎,乙型 /
- 受体,Notch /
- CD4阳性T淋巴细胞 /
- 白细胞介素类
Abstract: Objective To investigate the influence of Notch signaling pathway inhibition on interleukin- 22( IL- 22) secreted by CD4~+T cells in patients with hepatitis B,and to elaborate on the role of the Notch- IL- 22 signaling pathway in the pathogenesis of hepatitis B.Methods A total of 45 previously untreated patients with hepatitis B who visited and were hospitalized in Tangdu Hospital from July 2013 to December 2014 were enrolled,and among these patients,13 had acute hepatitis B( AHB) and 32 had chronic hepatitis B( CHB). Another20 healthy volunteers were enrolled as normal control( NC) group. CD4~+T cells were isolated,and quantitative real- time PCR was used to measure the mRNA expression of Notch1 and Notch2. CD4~+T cells were stimulated by anti- CD3 antibody or HBV core peptide library and the Notch signaling pathway inhibitor DAPT was added. Quantitative real- time PCR was used to measure the mRNA expression of IL-22 in cells,and ELISA was used to measure the level of IL- 22 secretory protein in supernatant. The Kruskal- Wallis H test was used for statistical analysis of data between groups,and the Dunn's multiple test was used for data comparison between any two groups. Results The mRNA expression of Notch1 in CD4~+T cells in CHB patients was about 2 times that in NCs( Z = 7. 708,P = 0. 018),and the mRNA expression of Notch2 in AHB and CHB patients was more than 10 times that in NCs( Z = 9. 643 and 12. 90,both P < 0. 000 1). Inhibition of the Notch signaling pathway did not influence the mRNA expression of IL- 22 in cultured CD4~+T cells,but significantly reduced the secretion of non- specific IL- 22 in NCs( Z = 5. 068,P = 0. 015),AHB patients( Z = 5. 203,P = 0. 016),and CHB patients( Z = 2. 892,P = 0. 047). Conclusion Inhibition of the Notch signaling pathway can block IL- 22 secretion by non- specific CD4~+T cells,suggesting that the Notch- IL- 22 signaling pathway may promote non- specific inflammatory response in HBV infection.-
Key words:
- hepatitis B /
- receptors /
- Notch /
- CD4-positive T-lymphocytes
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[1]ZHANG Y,COBLEIGH MA,LIAN JQ,et al.A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus[J].Gastroenterology,2011,141(5):1897-1906. [2]ALAM MS,MAEKAWA Y,KITAMURA A,et al.Notch signaling drives IL-22 secretion in CD4+T cells by stimulating the aryl hydrocarbon receptor[J].Proc Natl Acad Sci U S A,2010,107(13):5943-5948. [3] Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B(2010 version)[J].Chin JHepatol,2011,19(1):13-24.(in Chinese)中华医学会肝病学分会、感染病分会.慢性乙型肝炎防治指南(2010年版)[J].中华肝脏病杂志,2011,19(1):13-24. [4]COBLEIGH MA,ROBEK MD.Protective and pathological properties of IL-22 in liver disease:implications for viral hepatitis[J].Am JPathol,2013,182(1):21-28. [5]DUDAKOV JA,HANASH AM,van den BRINK MR.Interleukin-22:immunobiology and pathology[J].Annu Rev Immunol,2015,33:747-785. [6]XIANG X,GUI H,KING NJ,et al.IL-22 and non-ELR-CXCchemokine expression in chronic hepatitis B virus-infected liver[J].Immunol Cell Biol,2012,90(6):611-619. [7]HAO C,WANG J,KANG W,et al.Kinetics of Th17 cytokines during telbivudine therapy in patients with chronic hepatitis B[J].Viral Immunol,2013,26(5):336-342. [8]FEI Y,CHEN Y,WU WY.Research advances in relationship between interleukins and hepatitis B virus infection[J].J Chin Hepatol,2014,30(2):174-178.(in Chinese)费筠,陈月,吴文苑.白细胞介素与HBV感染的关系[J].临床肝胆病杂志,2014,30(2):174-178. [9]WANG L,WANG CM,HOU LH,et al.Disruption of the transcription factor recombination signal-binding protein-J kappa(RBP-J)leads to veno-occlusive disease and interfered liver regeneration in mice[J].Hepatology,2009,49(1):268-277. [10]PEI J,TANG Z,ZANG G,et al.Blockage of Notch1 signaling modulates the T-helper(Th)1/Th2 cell balance in chronic hepatitis B patients[J].Hepatol Res,2010,40(8):799-805. [11]VELDHOEN M,HIROTA K,WESTENDORF AM,et al.The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins[J].Nature,2008,453(7191):106-109. [12]LEE JS,CELLA M,MCDONALD KG,et al.AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch[J].Nat Immunol,2011,13(2):144-151. [13]JIA L,WU C.The biology and functions of Th22 cells[J].Adv Exp Med Biol,2014,841:209-230.
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