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Impact of STAT4 gene silencing on the expression profile of proteins in EL-4 cells

  • Articles/Immunology
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Chinese Science Bulletin

Abstract

The signal transducers and activators of transcription (STATs) have diverse biological functions and are involved in cell differentiation, proliferation, development, apoptosis and inflammation. Several constitutively activated STATs have been observed in a wide variety of human cancer cell lines and primary tumor cells, including blood malignancies and solid neoplasias. Although regulatory T (Treg) cells induce immune tolerance by suppressing host immune responses against self- or nonself-antigens, thus playing critical roles in preventing autoimmune diseases, they might inhibit antitumor immunity and promote tumor growth. Our previous findings suggest that the supernatant from STAT4-silenced tumor cell culture can significantly increase the ratio of CD4+ CD25+ Foxp3+ regulatory T cells among splenic cells in vitro, when compared to that from normal tumor cell culture. In the present study, we identified that the mouse lymphoma cell line EL-4 expressed a high level of STAT4, and silencing of STAT4 by siRNA did not change the expression levels of TGF-β and IL-10 in EL-4 cells. Two-dimensional electrophoresis was conducted to examine the difference of expression profiles of proteins between normal and STAT4-silenced EL4 cells. Some of the protein which has been changed may induce CD4+ CD25+ Foxp3+ regulatory T cells in vitro.

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References

  1. Pfeifer A C, Timmer J, Klingmüller U. Systems biology of JAK/STAT signaling. Essays Biochem, 2008, 45: 109–120

    Article  Google Scholar 

  2. Wuest T Y, Willette-Brown J, Durum S K, et al. The influence of IL-2 family cytokines on activation and function of naturally occurring regulatory T cells. J Leukoc Biol, 2008, 84: 973–980

    Article  Google Scholar 

  3. Mitchell T J, John S. Signal transducer and activator of transcription (STAT) signaling and T-cell lymphomas. Immunology, 2005, 114: 301–312

    Article  Google Scholar 

  4. Kim H S, Lee M S. STAT1 as a key modulator of cell death. Cell Signal, 2007, 19: 454–465

    Article  Google Scholar 

  5. Uddin S, Platanias L C. Mechanisms of type-I interferon signal transduction. J Biochem Mol Biol, 2004, 37: 635–641

    Google Scholar 

  6. Schindler C, Levy D E, Decker T. JAK-STAT signaling: From interferons to cytokines. J Biol Chem, 2007, 282: 20059–20063

    Article  Google Scholar 

  7. Wurster A L, Tanaka T, Grusby M J. The biology of Stat4 and Stat6. Oncogene, 2000, 19: 2577–2584

    Article  Google Scholar 

  8. WANG R F. Regulatory T cells and innate immune regulation in tumor immunity. Springer Semin Immun, 2006, 28: 17–23

    Article  Google Scholar 

  9. Wang Y, LI Y H, LI X J, et al. Functional analysis of STAT 4 in tumor immunity by inhibitory JAK/STAT in vitro (in Chinese). Acta Scient Nat Univ Nankaiensis (Nat Sci Ed), 2007, 40:102–105

    Google Scholar 

  10. Liu V C, Wong L Y, Jang T, et al. Tumor Evasion of the Immune System by Converting CD4+ CD25 T Cells into CD4+ CD25+ T Regulatory Cells: Role of Tumor-Derived TGF-β. J Immunol, 2007, 178: 2883–2892

    Google Scholar 

  11. Horwitz D A, Zheng S G, Gray J D. The role of the combination of IL-2 and TGF-β or IL-10 in the generation and function of CD4+ CD25+ and CD8+ regulatory T cell subsets. J Leukoc Biol, 2003, 74: 471–478

    Article  Google Scholar 

  12. Sugawara I, Yamada H, Mizuno S. Relative importance of STAT4 in murine tuberculosis. J Med Microbiol, 2003, 52: 29–34

    Article  Google Scholar 

  13. Suto A, Nakajima H, Tokumasa N, et al. Murine plasmacytoid dendritic cells produce IFN-γ upon IL-4 stimulation. J Immunol, 2005, 175: 5681–5689

    Google Scholar 

  14. Boyton R J, Davies S, Marden C, et al. Stat4-null non-obese diabetic mice: protection from diabetes and experimental allergic encephalomyelitis, but with concomitant epitope spread. Int Immunol, 2005, 17: 1157–1165

    Article  Google Scholar 

  15. Arya M, Shergill IS, Williamson M, et al. Basic principles of realtime quantitative PCR. Expert Rev Mol Diagn, 2005, 5: 209–219

    Article  Google Scholar 

  16. Fehervari Z, Sakaguchi S. Development and function of CD25+ CD4+ regulatory T cells. Curr Opin Immunol, 2004, 16: 203–208

    Article  Google Scholar 

  17. Schabowsky R H, Madireddi S, Sharma R, et al. Targeting CD4+ CD25+ FoxP3+ regulatory T cells for the augmentation of cancer immunotherapy. Curr Opin Investig Drugs, 2007, 8: 1002–1008

    Google Scholar 

  18. Ralainirina N, Poli A, Michel T, et al. Control of NK cell functions by CD4+ CD25+ regulatory T cells. J Leukoc Biol, 2007, 81: 144–153

    Article  Google Scholar 

  19. Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance. Cell, 2008, 133: 775–787

    Article  Google Scholar 

  20. Grant L R, Yao Z J, Hedrich C M, et al. Stat4-dependent, T-bet-independent regulation of IL-10 in NK cells. Genes Immun, 2008, 9: 316–327

    Article  Google Scholar 

  21. Collison L W, Workman C J, Kuo T T, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature, 2007, 450: 566–569

    Article  Google Scholar 

Download references

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Correspondence to Yue Wang.

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Supported by the National Key Basic Research and Development Program of China (Grant No. 2007CB914804), National High Technology Research and Development Program of China (Grant No. 2007AA021010), Foundation of the Ministry of Education of China for Returned Scholars, Key Project of the Science & Technology Pillar Program of Tianjin (Grant No. 07ZCKFSH03700), and Innovative Research Foundation of Nankai University

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Wei, X., Ni, H., Wang, Q. et al. Impact of STAT4 gene silencing on the expression profile of proteins in EL-4 cells. Chin. Sci. Bull. 54, 3265–3270 (2009). https://doi.org/10.1007/s11434-009-0468-9

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  • DOI: https://doi.org/10.1007/s11434-009-0468-9

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