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Expression of cytokines in mouse hepatitis B virus X gene-transfected model

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Summary

The expression profile in the mouse hepatitis B virus X (HBx)-transfected model was investigated in order to lay a foundation for further study on the implication of cytokines expression in hepatitis B virus (HBV) infection. Hydrodynamic injection method via the tail vein was used to establish the animal HBx-transfected model. By using microassay, the differential expression of gene in each group was analyzed, which was further confirmed by using real-time PCR and semi-quantitative PCR. Most of chemokine genes such as Ccl2, Ccl5, Ccl9, MIG and IP-10 were up-regulated in the HBx-transfected mouse model versus the control mice, which was coincided with the microarray results. Western blotting and immunohistochemistry were applied to detect the expression of MIG and IP-10 in the liver tissues. Simultaneously, ELISA was adopted to measure the content of IFN-γ in the liver tissues. DNA microassay revealed that the expression of 611 genes changed in HBx-transfected mice as compared with that in pCMV-tag2B-transfected mice, and most of the screened chemokines were up-regulated (including MIG and IP-10). Additionally, IFN-γ protein levels were increased by 20.7% (P<0.05) in pCMV-tag2B-HBx-transfected mice as compared with the untreated mice. IFN-γ protein levels were reduced by 53.9% (P<0.05) in pCMV-tag2B-transfected mice as compared with the untreated mice, which was consistent with the up-regulation of MIG and IP-10. It was suggested HBx transfection could induce the expression of MIG and IP-10 in the liver tissues, which might play the roles in HBV-related liver immunity and cytokines-mediated antiviral effect.

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References

  1. Ganem D, Varmus HE. The molecular biology of the hepatitis B viruses. Annu Rev Biochem, 1987,56:651–693

    Article  PubMed  CAS  Google Scholar 

  2. Yang PL, Althage A, Chung J, et al. Hydrodynamic injection of viral DNA: A mouse model of acute hepatitis B virus infection. P Natl Acad Sci USA, 2002,99(21):13825–3830

    Article  CAS  Google Scholar 

  3. Hu ZY, Zhang ZS, Kim JW, et al. Altered proteolysis and global gene expression in hepatitis B virus X transgenic mouse Liver. J Virol, 2006,80(3):1405–1413

    Article  PubMed  CAS  Google Scholar 

  4. Kuo CY, Wang JC, Wu CC, et al. Effects of hepatitis B virus X protein (HBx) on cell-growth inhibition in a CCL13-HBx stable cell line. Intervirology, 2008,51(1):26–32

    Article  PubMed  CAS  Google Scholar 

  5. Feitelson MA, Sun B, Satiroglu TNL, et al. Genetic mechanisms of hepatocarcinogenesis. Oncogene, 2002,21(16):2593–2604

    Article  PubMed  CAS  Google Scholar 

  6. Murakami S. Hepatitis B virus X protein: a multifunctional viral regulator. J Gastroenterol, 2001,36(10):651–660

    Article  PubMed  CAS  Google Scholar 

  7. Ma J, Sun T, Park S, et al. The role of hepatitis B virus X protein is related to its differential intracellular localization. Acta Biochim Biophys Sin, 2011,43(8):583–588

    Article  PubMed  CAS  Google Scholar 

  8. Xia LM, Huang WJ, Wu JG, et al. HBx protein induces expression of MIG and increases migration of leukocytes through activation of NF-kappa B. Virology, 2009,385(2):335–342

    Article  PubMed  CAS  Google Scholar 

  9. Zhou Y, Wang S, Ma JW, et al. Hepatitis B virus protein X-induced expression of the CXC chemokine IP-10 is mediated through activation of NF-kappa B and increases migration of leukocytes. J Biol Chem, 2010,285(16):12 159–12 168

    CAS  Google Scholar 

  10. Pan X, Cao H, Lu J, et al. Interleukin-32 expression induced by hepatitis B virus protein X is mediated through activation of NF-κB. Mol Immunol, 2011,48(12–13):1573–1577

    Article  PubMed  CAS  Google Scholar 

  11. Zhang X, You X, Wang Q, et al. Hepatitis B virus X protein drives multiple cross-talk cascade loops involving NF-κB, 5-LOX, OPN and Capn4 to promote cell migration. PLoS One, 2012,7(2):31 458

    Google Scholar 

  12. Xu Q, Pan X, Shu X, et al. Increased interleukin-32 expression in chronic hepatitis B virus-infected liver. J Infect, 2012,65(4):336–342

    Article  PubMed  Google Scholar 

  13. Kakimi K, Lane TE, Wieland S, et al. Blocking chemokine responsive to gamma-2/interferon (IFN)-gamma inducible protein and monokine induced by IFN-gamma activity in vivo reduces the pathogenetic but not the antiviral potential of hepatitis B virus-specific cytotoxic T lymphocyte. J Exp Med, 2001,194(12):1755–1766

    Article  PubMed  CAS  Google Scholar 

  14. Barone M, Spano D, D’Apolito M, et al. Gene expression analysis in HBV transgenic mouse liver: a model to study early events related to hepatocarcinogenesis. Mol Med, 2006,12(4–6):115–123

    PubMed  CAS  Google Scholar 

  15. Maguire HF, Hoeffler JP, Siddiqui A. HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions. Science, 1991,252(5007):842–844

    Article  PubMed  CAS  Google Scholar 

  16. Lin Y, Nomura T, Cheong JH, et al. Hepatitis B virus X protein is a transcriptional modulator that communicates with transcription factor IIB and the RNA polymerase II subunit 5. J Biol Chem, 1997,272(11):7132–7139

    Article  PubMed  CAS  Google Scholar 

  17. Shamay M, Barak O, Doitsh G, et al. Hepatitis B virus pX interacts with HBXAP, a PHD finger protein to coactivate transcription. J Biol Chem, 2002,277(12):9982–9988

    Article  PubMed  CAS  Google Scholar 

  18. Xia L, Tian D, Huang W, et al. Upregulation of IL-23 expression in patients with chronic hepatitis B is mediated by the HBx/ERK/NF-κB Pathway. J Immunol, 2012,188(2):753–764

    Article  PubMed  CAS  Google Scholar 

  19. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med, 2006,354(6):610–621

    Article  PubMed  CAS  Google Scholar 

  20. Maini MK, Boni C, Lee CK, et al. The role of virus-specific CD8 (+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med, 2000,191(8):1269–1280

    Article  PubMed  CAS  Google Scholar 

  21. Xiang X, Gui H, King NJ, et al. IL-22 and non-ELR-CXC chemokine expression in chronic hepatitis B virus-infected liver. Immunol Cell Biol, 2012,90(6):611–619

    Article  PubMed  CAS  Google Scholar 

  22. Pan CJ, Wu HL, Kuo SF, et al. Serum interleukin 6 level correlates with outcomes of acute exacerbation of chronic hepatitis B. Hepatol Int, 2012,6(3):591–597

    Article  Google Scholar 

  23. Clark EA, Golub TR, Lander ES, et al. Genomic analysis of metastasis reveals an essential role for RhoC. Nature, 2000,406(6795):536–540

    Article  Google Scholar 

  24. Nestl A, Von Stein OD, Zatloukal K, et al. Gene expression patterns associated with the metastatic phenotype in rodent and human tumors. Cancer Res, 2001,61(4):1569–1577

    PubMed  CAS  Google Scholar 

  25. MacDonald TJ, Brown KM, LaFleur B, et al. Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat Genet, 2001,29(2):143–152

    Article  PubMed  CAS  Google Scholar 

  26. Khanna C, Khan J, Nguyen P, et al. Metastasis-associated differences in gene expression in a murine model of osteosarcoma. Cancer Res, 2001,61(9):3750–3759

    PubMed  CAS  Google Scholar 

  27. Ma J, Huang C, Yao X, et al. Inhibition of hepatitis B virus and induction of hepatoma cell apoptosis by ASGPR-directed delivery of shRNAs. PLoS ONE, 2012,7(10):e46096

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Immunology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Li-fang Sun  (孙丽芳), Chuan Shi  (史 川), Lu Yuan  (袁 璐), Xin-xin Yao  (姚欣欣), Jing-wei Ma  (马婧薇), Chun-mei Huang  (黄春梅), Hui-fen Zhu  (朱慧芬), Ping Lei  (雷 萍) & Guan-xin Shen  (沈关心)

  2. Department of Laboratory, Huazhong University of Science and Technology, Wuhan, 430022, China

    Li-fang Sun  (孙丽芳)

  3. Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Yun Sun  (孙 云)

Authors
  1. Li-fang Sun  (孙丽芳)
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  2. Chuan Shi  (史 川)
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  3. Lu Yuan  (袁 璐)
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  4. Yun Sun  (孙 云)
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  5. Xin-xin Yao  (姚欣欣)
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  6. Jing-wei Ma  (马婧薇)
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  7. Chun-mei Huang  (黄春梅)
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  8. Hui-fen Zhu  (朱慧芬)
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  9. Ping Lei  (雷 萍)
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  10. Guan-xin Shen  (沈关心)
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Corresponding author

Correspondence to Guan-xin Shen  (沈关心).

Additional information

This project was supported by grants from Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1131) and State Project on Major Infectious Diseases Prevention Grant (No. 2012ZX10002006-003).

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Sun, Lf., Shi, C., Yuan, L. et al. Expression of cytokines in mouse hepatitis B virus X gene-transfected model. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 172–177 (2013). https://doi.org/10.1007/s11596-013-1092-0

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  • DOI: https://doi.org/10.1007/s11596-013-1092-0

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