Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Nov 22;91(24):11641–11645. doi: 10.1073/pnas.91.24.11641

Regulatory elements and transcription factors controlling basal and cytokine-induced expression of the gene encoding intercellular adhesion molecule 1.

J Hou 1, V Baichwal 1, Z Cao 1
PMCID: PMC45287  PMID: 7972116

Abstract

The gene encoding intercellular adhesion molecule 1 (ICAM-1) is transcriptionally induced in response to inflammatory and immunomodulatory cytokines. To investigate the mechanisms controlling ICAM-1 gene expression, we have identified regulatory DNA sequences responsible for maintaining basal and mediating induced transcription in response to tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). Regulatory elements centered 115, 60, and 40 bp upstream from the ICAM-1 transcription start site were implicated in cytokine-independent gene expression. Regulatory elements dedicated to TNF-alpha and IFN-gamma were identified 190 and 90 bp, respectively, upstream from the ICAM-1 transcription start site. A combination of mutagenesis and DNA-binding assays revealed that the TNF-alpha response element is composite, consisting of binding sites for both C/EBP and NF-kappa B. The IFN-gamma response element behaved as a simple regulatory element that selectively binds to an IFN-gamma-inducible activity composed, at least in part, of p91. These observations provide a framework for understanding how extracellular signals dynamically regulate the adhesive properties of mammalian cells.

Full text

PDF
11641

Images in this article

11642Image
on p.11642
11643Image
on p.11643
11644Image
on p.11644
11644Image
on p.11644

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baeuerle P. A., Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179. doi: 10.1146/annurev.iy.12.040194.001041. [DOI] [PubMed] [Google Scholar]
  2. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  3. Cao Z., Umek R. M., McKnight S. L. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991 Sep;5(9):1538–1552. doi: 10.1101/gad.5.9.1538. [DOI] [PubMed] [Google Scholar]
  4. Czech W., Krutmann J., Budnik A., Schöpf E., Kapp A. Induction of intercellular adhesion molecule 1 (ICAM-1) expression in normal human eosinophils by inflammatory cytokines. J Invest Dermatol. 1993 Apr;100(4):417–423. doi: 10.1111/1523-1747.ep12472082. [DOI] [PubMed] [Google Scholar]
  5. Degitz K., Li L. J., Caughman S. W. Cloning and characterization of the 5'-transcriptional regulatory region of the human intercellular adhesion molecule 1 gene. J Biol Chem. 1991 Jul 25;266(21):14024–14030. [PubMed] [Google Scholar]
  6. Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
  7. Gerritsen M. E., Bloor C. M. Endothelial cell gene expression in response to injury. FASEB J. 1993 Apr 1;7(6):523–532. doi: 10.1096/fasebj.7.6.8472891. [DOI] [PubMed] [Google Scholar]
  8. Gerritsen M. E., Kelley K. A., Ligon G., Perry C. A., Shen C. P., Szczepanski A., Carley W. W. Regulation of the expression of intercellular adhesion molecule 1 in cultured human endothelial cells derived from rheumatoid synovium. Arthritis Rheum. 1993 May;36(5):593–602. doi: 10.1002/art.1780360504. [DOI] [PubMed] [Google Scholar]
  9. Greenlund A. C., Farrar M. A., Viviano B. L., Schreiber R. D. Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91). EMBO J. 1994 Apr 1;13(7):1591–1600. doi: 10.1002/j.1460-2075.1994.tb06422.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grilli M., Chiu J. J., Lenardo M. J. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol. 1993;143:1–62. doi: 10.1016/s0074-7696(08)61873-2. [DOI] [PubMed] [Google Scholar]
  11. Hynes R. O., Lander A. D. Contact and adhesive specificities in the associations, migrations, and targeting of cells and axons. Cell. 1992 Jan 24;68(2):303–322. doi: 10.1016/0092-8674(92)90472-o. [DOI] [PubMed] [Google Scholar]
  12. Isobe M., Yagita H., Okumura K., Ihara A. Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Science. 1992 Feb 28;255(5048):1125–1127. doi: 10.1126/science.1347662. [DOI] [PubMed] [Google Scholar]
  13. Isshiki H., Akira S., Sugita T., Nishio Y., Hashimoto S., Pawlowski T., Suematsu S., Kishimoto T. Reciprocal expression of NF-IL6 and C/EBP in hepatocytes: possible involvement of NF-IL6 in acute phase protein gene expression. New Biol. 1991 Jan;3(1):63–70. [PubMed] [Google Scholar]
  14. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  15. Juan T. S., Wilson D. R., Wilde M. D., Darlington G. J. Participation of the transcription factor C/EBP delta in the acute-phase regulation of the human gene for complement component C3. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2584–2588. doi: 10.1073/pnas.90.7.2584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kukielka G. L., Hawkins H. K., Michael L., Manning A. M., Youker K., Lane C., Entman M. L., Smith C. W., Anderson D. C. Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium. J Clin Invest. 1993 Sep;92(3):1504–1516. doi: 10.1172/JCI116729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988 Jul;2(7):786–800. doi: 10.1101/gad.2.7.786. [DOI] [PubMed] [Google Scholar]
  18. LeClair K. P., Blanar M. A., Sharp P. A. The p50 subunit of NF-kappa B associates with the NF-IL6 transcription factor. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8145–8149. doi: 10.1073/pnas.89.17.8145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Look D. C., Pelletier M. R., Holtzman M. J. Selective interaction of a subset of interferon-gamma response element-binding proteins with the intercellular adhesion molecule-1 (ICAM-1) gene promoter controls the pattern of expression on epithelial cells. J Biol Chem. 1994 Mar 25;269(12):8952–8958. [PubMed] [Google Scholar]
  20. Matsusaka T., Fujikawa K., Nishio Y., Mukaida N., Matsushima K., Kishimoto T., Akira S. Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10193–10197. doi: 10.1073/pnas.90.21.10193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McEver R. P. Leukocyte interactions mediated by selectins. Thromb Haemost. 1991 Jul 12;66(1):80–87. [PubMed] [Google Scholar]
  22. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  24. Ron D., Brasier A. R., McGehee R. E., Jr, Habener J. F. Tumor necrosis factor-induced reversal of adipocytic phenotype of 3T3-L1 cells is preceded by a loss of nuclear CCAAT/enhancer binding protein (C/EBP). J Clin Invest. 1992 Jan;89(1):223–233. doi: 10.1172/JCI115566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schindler C., Shuai K., Prezioso V. R., Darnell J. E., Jr Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science. 1992 Aug 7;257(5071):809–813. doi: 10.1126/science.1496401. [DOI] [PubMed] [Google Scholar]
  26. Shuai K., Stark G. R., Kerr I. M., Darnell J. E., Jr A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science. 1993 Sep 24;261(5129):1744–1746. doi: 10.1126/science.7690989. [DOI] [PubMed] [Google Scholar]
  27. Simmons D., Makgoba M. W., Seed B. ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature. 1988 Feb 18;331(6157):624–627. doi: 10.1038/331624a0. [DOI] [PubMed] [Google Scholar]
  28. Stein B., Baldwin A. S., Jr Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-kappa B. Mol Cell Biol. 1993 Nov;13(11):7191–7198. doi: 10.1128/mcb.13.11.7191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thomson A. W., Satoh S., Nüssler A. K., Tamura K., Woo J., Gavaler J., van Thiel D. H. Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes. Clin Exp Immunol. 1994 Jan;95(1):83–90. doi: 10.1111/j.1365-2249.1994.tb06019.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Voraberger G., Schäfer R., Stratowa C. Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5'-regulatory region. Induction by cytokines and phorbol ester. J Immunol. 1991 Oct 15;147(8):2777–2786. [PubMed] [Google Scholar]
  31. Wegner C. D., Gundel R. H., Reilly P., Haynes N., Letts L. G., Rothlein R. Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science. 1990 Jan 26;247(4941):456–459. doi: 10.1126/science.1967851. [DOI] [PubMed] [Google Scholar]
  32. Wertheimer S. J., Myers C. L., Wallace R. W., Parks T. P. Intercellular adhesion molecule-1 gene expression in human endothelial cells. Differential regulation by tumor necrosis factor-alpha and phorbol myristate acetate. J Biol Chem. 1992 Jun 15;267(17):12030–12035. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES