Skip to main content

Advertisement

SpringerLink
Log in

HSF1 regulates expression of G-CSF through the binding element for NF-IL6/CCAAT enhancer binding protein beta

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Heat shock factor 1 (HSF1) is the major heat shock transcription factor and plays an essential role in mediating the cellular response to physiological and environmental stress. We found that LPS-induced expression of the granulocyte-colony stimulating factor (G-CSF) gene was upregulated in HSF1 knock-out (HSF1−/−) mice using a gene array. In order to determine whether and how HSF1 regulates the induced expression of G-CSF, mRNA, and protein levels of G-CSF were detected by Northern blotting and ELISA, the promoter of G-CSF was analyzed with an online transcription element search system and the transcriptional activity of the G-CSF promoter was analyzed by EMSA and a reporter gene assay. The results showed that transcription and protein secretion of G-CSF induced by LPS are both inhibited by HSF1. Three high affinity binding sites for NF-IL6/CCAAT enhancer binding protein beta, but no heat shock element, were identified in the core promoter of G-CSF. The DNA-binding capability of NF-IL6 to the G-CSF promoter was reinforced by LPS but not influenced by heat shock or HSF1. However, HSF1 was observed to bind to the binding sites of NF-IL6 in the G-CSF promoter. The transcriptional activity of the G-CSF promoter was enhanced by LPS or NF-IL6 and inhibited by HSF1 in a dose dependent manner. We conclude that HSF1 regulates expression of G-CSF through binding to the NF-IL6-binding element.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

HSF1:

Heat shock factor 1

G-CSF:

Granulocyte-colony stimulating factor

NF-IL6:

Nuclear factor-interleukin 6

LPS:

Lipopolysaccharide

References

  1. Sorger PK (1991) Heat shock factor and the heat shock response. Cell 65(3):363–366

    Article  PubMed  CAS  Google Scholar 

  2. Voellmy R (1994) Transduction of the stress signal and mechanisms of transcriptional regulation of heat shock/stress protein gene expression in higher eukaryotes. Crit Rev Eukaryot Gene Expr 4(4):357–401

    PubMed  CAS  Google Scholar 

  3. Perisic O, Xiao H, Lis JT (1989) Stable binding of drosophila heat shock factor to head-to-head and tail-to-tail repeats of a conserved 5 bp recognition unit. Cell 59(5):797–806

    Article  PubMed  CAS  Google Scholar 

  4. Cahill CM, Waterman WR, Xie Y, Auron PE, Calderwood SK (1996) Transcriptional repression of the prointerleukin 1 beta gene by heat shock factor 1. J Biol Chem 271(40):24874–24879

    PubMed  CAS  Google Scholar 

  5. Singh IS, He JR, Calderwood S, Hasday JD (2002) A high affinity hsf-1 binding site in the 5′-untranslated region of the murine tumor necrosis factor-alpha gene is a transcriptional repressor. J Biol Chem 277(7):4981–4988

    Article  PubMed  CAS  Google Scholar 

  6. Xie Y, Zhong R, Chen C, Calderwood SK (2003) Heat shock factor 1 contains two functional domains that mediate transcriptional repression of the c-fos and c-fms genes. J Biol Chem 278(7):4687–4698

    Article  PubMed  CAS  Google Scholar 

  7. FX Yu, Zhang HL, Chen GW, Wang QP, Shi YZ, Liu Y, Liang QJ, Xiao X (2006) Screen of inflammatory genes regulated by heat shock factor 1 and corrobration with socs3 gene. J Central South University 31:167–173

    Google Scholar 

  8. Demetri GD, Griffin JD (1991) Granulocyte colony-stimulating factor and its receptor. Blood 78(11):2791–2808

    PubMed  CAS  Google Scholar 

  9. Weiss M, Fischer G, Barth E, Boneberg E, Schneider EM, Georgieff M, Hartung T (2001) Dissociation of lps-induced monocytic ex vivo production of granulocyte colony-stimulating factor (g-csf) and tnf-alpha in patients with septic shock. Cytokine 13(1):51–54

    Article  PubMed  CAS  Google Scholar 

  10. Vandermolen DT, Kauma SW, Turner TT (1996) Interleukin-1 beta and tumor necrosis factor-alpha stimulate granulocyte colony-stimulating factor production by placental villous core mesenchymal cells. J Soc Gynecol Investig 3(4):172–178

    Article  PubMed  CAS  Google Scholar 

  11. Numasaki M, Takahashi H, Tomioka Y, Sasaki H (2004) Regulatory roles of il-17 and il-17f in g-csf production by lung microvascular endothelial cells stimulated with il-1beta and/or tnf-alpha. Immunol Lett 95(1):97–104

    Article  PubMed  CAS  Google Scholar 

  12. Nishizawa M, Nagata S (1992) Cdna clones encoding leucine-zipper proteins which interact with g-csf gene promoter element 1-binding protein. FEBS Lett 299(1):36–38

    Article  PubMed  CAS  Google Scholar 

  13. Nishizawa M, Wakabayashi-Ito N, Nagata S (1991) Molecular cloning of cdna and a chromosomal gene encoding gpe1-bp, a nuclear protein which binds to granulocyte colony-stimulating factor promoter element 1. FEBS Lett 282(1):95–97

    Article  PubMed  CAS  Google Scholar 

  14. Nishizawa M, Nagata S (1990) Regulatory elements responsible for inducible expression of the granulocyte colony-stimulating factor gene in macrophages. Mol Cell Biol 10(5):2002–2011

    PubMed  CAS  Google Scholar 

  15. Kiehntopf M, Herrmann F, Brach MA (1995) Functional nf-il6/ccaat enhancer-binding protein is required for tumor necrosis factor alpha-inducible expression of the granulocyte colony-stimulating factor (csf), but not the granulocyte/macrophage csf or interleukin 6 gene in human fibroblasts. J Exp Med 181(2):793–798

    Article  PubMed  CAS  Google Scholar 

  16. Akira S (1997) Il-6-regulated transcription factors. Int J Biochem Cell Biol 29(12):1401–1418

    Article  PubMed  CAS  Google Scholar 

  17. Akira S, Isshiki H, Sugita T, Tanabe O, Kinoshita S, Nishio Y, Nakajima T, Hirano T, Kishimoto T (1990) A nuclear factor for il-6 expression (nf-il6) is a member of a c/ebp family. EMBO J 9(6):1897–1906

    PubMed  CAS  Google Scholar 

  18. Edwards MR, Mukaida N, Johnson M, Johnston SL (2005) Il-1beta induces il-8 in bronchial cells via nf-kappab and nf-il6 transcription factors and can be suppressed by glucocorticoids. Pulm Pharmacol Ther 18(5):337–345

    Article  PubMed  CAS  Google Scholar 

  19. Yang Z, Wara-Aswapati N, Chen C, Tsukada J, Auron PE (2000) Nf-il6 (c/ebpbeta) vigorously activates il1b gene expression via a spi-1 (pu.1) protein-protein tether. J Biol Chem 275(28):21272–21277

    Article  PubMed  CAS  Google Scholar 

  20. Li Weber M, Giaisi M, Baumann S, Palfi K, Krammer PH (2004) Nf-kappa b synergizes with nf-at and nf-il6 in activation of the il-4 gene in t cells. Eur J Immunol 34(4):1111–1118

    Article  Google Scholar 

  21. McMillan DR, Xiao X, Shao L, Graves K, Benjamin IJ (1998) Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis. J Biol Chem 273(13):7523–7528

    Article  PubMed  CAS  Google Scholar 

  22. Mathew A, Shi Y, Jolly C, Morimoto RI (2000) Analysis of the mammalian heat-shock response. Inducible gene expression and heat-shock factor activity. Methods Mol Biol 99:217–255

    PubMed  CAS  Google Scholar 

  23. Xiao X, Zuo X, Davis AA, McMillan DR, Curry BB, Richardson JA, Benjamin IJ (1999) Hsf1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice. EMBO J 18(21):5943–5952

    Article  PubMed  CAS  Google Scholar 

  24. Xie Y, Chen C, Stevenson MA, Auron PE, Calderwood SK (2002) Heat shock factor 1 represses transcription of the il-1beta gene through physical interaction with the nuclear factor of interleukin 6. J Biol Chem 277(14):11802–11810

    Article  PubMed  CAS  Google Scholar 

  25. Nishizawa M, Tsuchiya M, Watanabe-Fukunaga R, Nagata S (1990) Multiple elements in the promoter of granulocyte colony-stimulating factor gene regulate its constitutive expression in human carcinoma cells. J Biol Chem 265(10):5897–5902

    PubMed  CAS  Google Scholar 

  26. Dunn SM, Coles LS, Lang RK, Gerondakis S, Vadas MA, Shannon MF (1994) Requirement for nuclear factor (nf)-kappa b p65 and nf-interleukin-6 binding elements in the tumor necrosis factor response region of the granulocyte colony-stimulating factor promoter. Blood 83(9):2469–2479

    PubMed  CAS  Google Scholar 

  27. Xie Y, Chen C, Stevenson MA, Hume DA, Auron PE, Calderwood SK (2002) Nf-il6 and hsf1 have mutually antagonistic effects on transcription in monocytic cells. Biochem Biophys Res Commun 291(4):1071–1080

    Article  PubMed  CAS  Google Scholar 

  28. Barth E, Fischer G, Schneider EM, Moldawer LL, Georgieff M, Weiss M (2002) Peaks of endogenous g-csf serum concentrations are followed by an increase in respiratory burst activity of granulocytes in patients with septic shock. Cytokine 17(5):275–284

    Article  PubMed  CAS  Google Scholar 

  29. Fialkow L, Fochesatto Filho L, Bozzetti MC, Milani AR, Rodrigues Filho EM, Ladniuk RM, Pierozan P, de Moura RM, Prolla JC, Vachon E, Downey GP (2006) Neutrophil apoptosis: A marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome. Crit Care 10(6):R155

    Article  PubMed  Google Scholar 

  30. Haley M, Parent C, Cui X, Kalil A, Fitz Y, Correa-Araujo R, Natanson C, Danner RL, Banks SM, Eichacker PQ (2005) Neutrophil inhibition with l-selectin-directed mab improves or worsens survival dependent on the route but not severity of infection in a rat sepsis model. J Appl Physiol 98(6):2155–2162

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the State Key Development Program for Basic Research of China (2007CB512007) and the National Natural Science Foundation of China (09JJ4012).

Author information

Authors and Affiliations

  1. Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, People’s Republic of China

    Lingli Zhang, Qiupeng Wang, Meidong Liu, Qiujuan Liang, Huali Zhang & Xianzhong Xiao

  2. Department of Intensive Care Unit, The Third Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, People’s Republic of China

    Mingshi Yang

Authors
  1. Lingli Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingshi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiupeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meidong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qiujuan Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huali Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xianzhong Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Huali Zhang or Xianzhong Xiao.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L., Yang, M., Wang, Q. et al. HSF1 regulates expression of G-CSF through the binding element for NF-IL6/CCAAT enhancer binding protein beta. Mol Cell Biochem 352, 11–17 (2011). https://doi.org/10.1007/s11010-010-0624-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-010-0624-1

Keywords

Search

Navigation