Skip to main content

Interleukin 1 (IL-1) Induces the Activation of Stat3

  • Chapter
Tissue Engineering, Stem Cells, and Gene Therapies

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 534))

Abstract

Interleukin-1 (IL-1) is involved in a variety of immune system activities, such as acute phase response, fever and cartilage breakdown. The acute phase response is a result of injury, virus or bacterial infection, all of which induce acute phase protein synthesis. Expression of the acute phase proteins is predominantly regulated by IL-1 and IL-6; however, the liver centrally regulates the acute-phase response by inducing the release of acute phase reactants (APRs). There are two classes of these acute phase reactants. IL-1 induces class 1 acute phase proteins, such as serum amyloid A and 1acid glycoprotein, synergistically, with or without IL-6. However, class 2 APRs, including various anti-proteases and 2-macroglobin, are induced only by IL-6. The promoters of some of the acute phase genes contain regulatory respond elements called acute phase response elements (APRE). APRE bind to transcription factors termed acute-phase response factor (AFRF) or to the signal transducer and activator of transcription 3, (Stat3). Additional types of regulatory elements found in promoters of APRs are CCAAT enhancer-binding protein (C/EBP) and nuclear factor-N3 (NF-NB) binding elements that bind to C/EBP family of transcription factors such as NF-IL6, C/EBPI and NF-NB respectively. IL-1 only activates NF-A8 and C/EBP transcription factors; however, IL-6 activates Stat3 molecules.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Dinarello, C.A., 1996, Biological basis for Interleukin 1 in diseases.Blood87, 2095–2147.

    Google Scholar 

  2. Shen, X., Tian, Z., Holtzman, M.J., and Gao, B., 2000, Cross-talk between interleukin lE and IL-6 signaling pathways: IL-1E selectively inhibits IL-6-activated signal transducer and activator of transcription factor 1 (STAT1) by a proteasome-dependent mechanism.Biochem. J.352, 913–919.

    Article  Google Scholar 

  3. Wilson, D.R., Juan, T.S., Wilde, M.D., Fey, G.H., and Darlington, G.J., 1990, A 58-basepair region of the human C3 gene confers synergistic inducibility by interleukin-1 and interleukinMol Cell Biol. 106181–6191.

    Google Scholar 

  4. Hocke, G.M., Barry, D., and Fey, G.H., 1992, Synergistic action of interleukin-6 and glucocorticoids is mediated by the interleukin-6 response element of the rat alpha 2 macroglobulin gene.Mol Cell Biol.12, 2282–94.

    Google Scholar 

  5. Wegenka, U.M., Lutticken, C., Buschmann, J., Yuan, J., Lottspeich., F., Muller-Esterl, W., Schindler, C., Roeb, E., Heinrich, P.C., and Horn, F., 1994, The interleukin-6activated acute phase response factor is antigenically and functionally related to members of the signal transducer and activator of transcription (STAT) family.Mol Cell Biol.14, 3186–96.

    Google Scholar 

  6. Akira, S., Isshiki, H., Sugita, T., Tanabe, O., Kinoshita, S., Nishio, Y., Nakajima, T., Hirano, T., and Kishimoto, T., 1990, A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J.9, 1897–906.

    Google Scholar 

  7. Rothwarf, D.M., and Karin, M., 1999, The NF-kappa E activation pathway: a paradigm in information transfer from membrane to nucleus.Sci STKE 5Review.

    Google Scholar 

  8. Auron P.E., 1998, The interleukin 1 receptor: ligand interactions and signal transduction.CytokineGrowth Factor Rev. 9, 221–37.

    Article  Google Scholar 

  9. Tsukada, J., Waterman, W.R., Koyama, Y., Webb, A.C., and Auron, P.E., 1996, A novel STAT-like factor mediates lipopolysaccharide, interleukin 1 (IL-1), and IL-6 signaling and recognizes a gamma interferon activation site-like element in the IL1E gene. Mol Cell Biol. 16, 2183–94.

    Google Scholar 

  10. Schumann, R.R., Kirschning, C.J., Unbehaun, A., Aberle, H.P., Knope, H.P., Lamping, N., and Herrmann, F. 1996, The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins. Mol. Cell Biol. 16, 3490–503.

    Google Scholar 

  11. Morton, N.M., de Groot, R.P., and Emilsson, V., 1999, Interleukin-1E activates a short STAT-3 isoform in clonal insulin-secreting cells. FEBS Lett. 442, 57–60.

    Article  Google Scholar 

  12. Zhang, Z., and Fuller, G.M., 2000, Interleukin lE inhibits interleukin 6-mediated rat $ fibrinogen gene expression.Hemostasis Thrombosis Vasc. Biol.96, 3466–3472.

    Google Scholar 

  13. Benkhart, E.M., Siedlar, M., Wedel, A., Werner, T., Ziegler-Heitbrock, H.W., 2000, Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression.J. Immunol.1651612–7.

    Google Scholar 

  14. Bromberg, J., 2002, Stat proteins and oncogenesis.J Clin Invest.109, 1139–42.

    Google Scholar 

  15. Schindler, C., and Darnell, J.E. Jr.1995, Transcriptional responses to polypeptide ligands: the JAK-STAT pathwayAnnu Rev Biochem.64621–51. Review.

    Article  Google Scholar 

  16. Akira, S., Nishio, Y., Inoue, M., Wang, X.J., Wei, S., Matsusaka, T., Yoshida, K., Sudo, T., Naruto, M., and Kishimoto, T.,1994, Molecular cloning of APRF, a novel IFNstimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 77, 63–71.

    Article  Google Scholar 

  17. Kuno, K., and Matsushima, K., 1994, The IL-1 receptor signaling pathway.J. Leukoc. Biol.56, 542–7. Review.

    Google Scholar 

  18. Yoo, J.Y., Wang, W., Desiderio, S., and Nathans, D., 2001, Synergistic activity of STAT3 and c-Jun at a specific array of DNA elements in the alpha 2-macroglobulin promoter. J. Biol. Chem. 276, 26421–9.

    Article  Google Scholar 

  19. Seidel, H.M., Milocco, L.H., Lamb, P., Darnell, J.E., Jr, Stein, R.B., and Rosen, J.,1995, Spacing of palindromic half sites as a determinant of selective STAT (signal transducers and activators of transcription) DNA binding and transcriptional activity. Proc. Natl. Acad. Sci. USA 92, 3041–3045.

    Article  Google Scholar 

  20. Wagner, B.J., Hayes, T.E., Hoban, C.J., and Cochran, B.H., 1990, The SIF binding element confers sis/PDGF inducibility onto the c-fos promoter. EMBO J. 9, 4477–84.

    Google Scholar 

  21. David, M., 1995, Trancription factors in interferon signaling. Pharm. Ther. 65, 149 161.

    Google Scholar 

  22. Zhong, Z., Wen, Z., and Darnell, J.E. Jr., 1994, Stat3:a stat family member activated by tyrosine phosphorylation in respons to EGF and IL-6. Science 264, 95–98.

    Article  Google Scholar 

  23. Schuringa, J.J., Schepers, H., Vellenga, E., and Kruijer, W., 2001, Ser727-dependent transcriptional activation by association of p300 with STAT3 upon IL-6 stimulation. FEBS Lett. 495, 71–6.

    Article  Google Scholar 

  24. Finidori, J., and Kelly, P.A., 1995, Cytokine receptor signalling through two novel families of transducer molecules: Janus kinases, and signal transducers and activators of transcription. J. Endocrinol. 147, 11–23.

    Article  Google Scholar 

  25. Wilks, A.F., and Oates, A.C., 1996, The JAK/STAT pathway. Cancer Surv. 27, 139–63.

    Google Scholar 

  26. Boulton, T.G., Zhong, Z., Wen, Z., Darnell, J.E. Jr, Stahl, N., and Yancopoulos, G.D., 1995, STAT3 activation by cytokines utilizing gp130 and related transducers involves a secondary modification requiring an H7-sensitive kinase. Proc. Natl. Acad. Sci. USA. 92, 6915–9.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Arman, A., Auron, P.E. (2003). Interleukin 1 (IL-1) Induces the Activation of Stat3. In: Elçin, Y.M. (eds) Tissue Engineering, Stem Cells, and Gene Therapies. Advances in Experimental Medicine and Biology, vol 534. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0063-6_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0063-6_22

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4907-5

  • Online ISBN: 978-1-4615-0063-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics