Home LiteratureArticle Details
PMID: 2405250 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Involvement of a NF-kappa B-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines.

Molecular and cellular biology ·Vol. 10 ·No. 2 ·1990-02-00 ·Pages 561-8

Shimizu H, Mitomo K, Watanabe T, Okamoto S, Yamamoto K

Abstract

Interleukin-6 (IL-6) is one of the major mediators of inflammation, and its expression is inducible by the other inflammatory lymphokines, interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). We demonstrate that a common IL-6 promoter element, termed inflammatory lymphokine-responsive element (ILRE), is important for induction of IL-6 gene expression by IL-1 and TNF-alpha despite possible differences in the mechanisms of action of these lymphokines. Remarkably, the ILRE sequence, located between -73 to -63 relative to the mRNA cap site, is highly homologous to NF-kappa B transcription factor-binding motifs and binds an IL-1-TNF-alpha-inducible nuclear factor; the sequence specificities, binding characteristics, and subcellular localizations of this factor are indistinguishable from those of NF-kappa B. In addition, mutations of the ILRE sequence which impair the binding of this nuclear factor abolished the induction of IL-6 gene expression by IL-1 and TNF-alpha in vivo. These results indicate that a nuclear factor indistinguishable from NF-kappa B is involved in the transcriptional activation of the IL-6 gene by IL-1 and TNF-alpha.

MeSH Terms
Animals Base Sequence Cell Nucleus/metabolism Chromosome Deletion Cloning, Molecular DNA/genetics,metabolism Gene Expression Regulation Gene Library Genes/drug effects Humans Inflammation Interleukin-1/pharmacology Interleukin-6/genetics L Cells/immunology Lymphokines/pharmacology Mice Molecular Sequence Data NF-kappa B Oligonucleotide Probes Plasmids Promoter Regions, Genetic Sequence Homology, Nucleic Acid Transcription Factors/metabolism Transfection Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Interleukin-1 Interleukin-6 Lymphokines NF-kappa B Oligonucleotide Probes Transcription Factors Tumor Necrosis Factor-alpha DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shimizu H
Department of Molecular Pathology, Cancer Research Institute, Ishikawa, Japan.
Mitomo K
Watanabe T
Okamoto S
Yamamoto K
References (58)
58 references, click to expand
  1. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment.
    Nucleic Acids Res. 1984 Jul 25;12(14):5707-17 PMID: 6589587
  2. Involvement of a cis-element that binds an H2TF-1/NF kappa B like factor(s) in the virus-induced interferon-beta gene expression.
    Nucleic Acids Res. 1989 May 11;17(9):3335-46 PMID: 2566973
  3. Cloning and characterization of the cDNAs for human and rabbit interleukin-1 precursor.
    Nucleic Acids Res. 1985 Aug 26;13(16):5869-82 PMID: 2994016
  4. A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes.
    Nature. 1986 Jan 9-15;319(6049):154-8 PMID: 3079885
  5. Cachectin and tumour necrosis factor as two sides of the same biological coin.
    Nature. 1986 Apr 17-23;320(6063):584-8 PMID: 3010124
  6. The human beta-interferon gene enhancer is under negative control.
    Cell. 1986 May 23;45(4):601-10 PMID: 3708688
  7. Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors.
    Cell. 1986 Aug 15;46(4):567-74 PMID: 3524858
  8. Multiple nuclear factors interact with the immunoglobulin enhancer sequences.
    Cell. 1986 Aug 29;46(5):705-16 PMID: 3091258
  9. Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts.
    Eur J Biochem. 1986 Sep 15;159(3):625-32 PMID: 3758081
  10. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism.
    Cell. 1986 Dec 26;47(6):921-8 PMID: 3096580
  11. Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines.
    EMBO J. 1986 Oct;5(10):2529-37 PMID: 3023045
  12. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin.
    Nature. 1986 Nov 6-12;324(6092):73-6 PMID: 3491322
  13. Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta 2 interferon involved.
    Proc Natl Acad Sci U S A. 1986 Dec;83(23):8957-61 PMID: 3538015
  14. Human beta 2 interferon and B-cell differentiation factor BSF-2 are identical.
    Science. 1987 Feb 13;235(4790):731-2 PMID: 3492764
  15. Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor.
    J Exp Med. 1987 Mar 1;165(3):914-9 PMID: 3493322
  16. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities.
    Lab Invest. 1987 Mar;56(3):234-48 PMID: 3029503
  17. Double-stranded RNA activates binding of NF-kappa B to an inducible element in the human beta-interferon promoter.
    EMBO J. 1989 Apr;8(4):1129-38 PMID: 2663471
  18. Multiple actions of interleukin 6 within a cytokine network.
    Immunol Today. 1988 May;9(5):137-9 PMID: 3076767
  19. Involvement of a common transcription factor in the regulated expression of IL-2 and IL-2 receptor genes.
    Int Immunol. 1989;1(1):43-9 PMID: 2518655
  20. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.
    Cell. 1987 Jun 19;49(6):729-39 PMID: 3034432
  21. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements.
    Cell. 1987 Jun 19;49(6):741-52 PMID: 3034433
  22. B cell growth modulating and differentiating activity of recombinant human 26-kd protein (BSF-2, HuIFN-beta 2, HPGF).
    EMBO J. 1987 May;6(5):1219-24 PMID: 3497029
  23. Recombinant human B cell stimulatory factor 2 (BSF-2/IFN-beta 2) regulates beta-fibrinogen and albumin mRNA levels in Fao-9 cells.
    FEBS Lett. 1987 Aug 31;221(1):18-22 PMID: 3305075
  24. Structural diversity of murine serum amyloid A genes. Evolutionary implications.
    J Immunol. 1987 Sep 1;139(5):1683-8 PMID: 3624868
  25. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells.
    Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251-5 PMID: 2444978
  26. Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of beta 2 interferon by human fibroblasts.
    J Exp Med. 1987 Nov 1;166(5):1300-9 PMID: 2824651
  27. c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore.
    Mol Cell Biol. 1987 Oct;7(10):3490-502 PMID: 3119989
  28. A cellular protein, activating transcription factor, activates transcription of multiple E1A-inducible adenovirus early promoters.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8355-9 PMID: 2960975
  29. Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene.
    EMBO J. 1987 Oct;6(10):2939-45 PMID: 3500852
  30. Transcriptional regulation of the interferon-beta 2/B cell differentiation factor BSF-2/hepatocyte-stimulating factor gene in human fibroblasts by other cytokines.
    J Immunol. 1988 Feb 1;140(3):974-7 PMID: 3276786
  31. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor.
    Cell. 1988 Apr 22;53(2):211-7 PMID: 3129195
  32. The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV.
    Cell. 1988 Jun 3;53(5):827-36 PMID: 2836068
  33. HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor.
    Nature. 1988 Jun 23;333(6175):776-8 PMID: 2838755
  34. Identification and purification of a human immunoglobulin-enhancer-binding protein (NF-kappa B) that activates transcription from a human immunodeficiency virus type 1 promoter in vitro.
    Proc Natl Acad Sci U S A. 1988 Jul;85(13):4700-4 PMID: 3133660
  35. Activation of the human "beta 2-interferon/hepatocyte-stimulating factor/interleukin 6" promoter by cytokines, viruses, and second messenger agonists.
    Proc Natl Acad Sci U S A. 1988 Sep;85(18):6701-5 PMID: 3045822
  36. Enhancement of cAMP levels and of protein kinase activity by tumor necrosis factor and interleukin 1 in human fibroblasts: role in the induction of interleukin 6.
    Proc Natl Acad Sci U S A. 1988 Sep;85(18):6802-5 PMID: 2842790
  37. Multiple biological activities are expressed by a mouse interleukin 6 cDNA clone isolated from bone marrow stromal cells.
    Proc Natl Acad Sci U S A. 1988 Oct;85(19):7099-103 PMID: 3262872
  38. Cyclic AMP induction of early adenovirus promoters involves sequences required for E1A trans-activation.
    Proc Natl Acad Sci U S A. 1988 Oct;85(19):7192-6 PMID: 2902626
  39. NF-kappa B protein purification from bovine spleen: nucleotide stimulation and binding site specificity.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8825-9 PMID: 2848241
  40. Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6.
    Mol Cell Biol. 1988 Aug;8(8):3546-9 PMID: 3264880
  41. Sequence requirement for specific interaction of an enhancer binding protein (EBP1) with DNA.
    Nucleic Acids Res. 1989 Jan 25;17(2):499-516 PMID: 2536920
  42. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  43. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  44. Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha.
    Nature. 1989 Feb 16;337(6208):661-3 PMID: 2537468
  45. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  46. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.
    Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 PMID: 6828386
  47. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene.
    Cell. 1983 Oct;34(3):865-79 PMID: 6313211
  48. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene.
    Cell. 1987 Apr 10;49(1):29-38 PMID: 2881624
  49. A cytokine network in human diploid fibroblasts: interactions of beta-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1.
    Mol Cell Biol. 1987 Jan;7(1):273-80 PMID: 3494192
  50. Binding of a nuclear factor to a regulatory sequence in the promoter of the mouse H-2Kb class I major histocompatibility gene.
    Mol Cell Biol. 1987 Jan;7(1):305-13 PMID: 3561391
  51. An inducible transcription factor activates expression of human immunodeficiency virus in T cells.
    Nature. 1987 Apr 16-22;326(6114):711-3 PMID: 3031512
  52. A common positive trans-acting factor binds to enhancer sequences in the promoters of mouse H-2 and beta 2-microglobulin genes.
    Proc Natl Acad Sci U S A. 1987 May;84(9):2653-7 PMID: 3554244
  53. Tumor necrosis factor alpha induces proteins that bind specifically to kappa B-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes.
    Proc Natl Acad Sci U S A. 1989 Apr;86(7):2331-5 PMID: 2494663
  54. 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):2336-40 PMID: 2494664
  55. The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction.
    Cell. 1989 Apr 21;57(2):287-94 PMID: 2495183
  56. Activation of HIV gene expression during monocyte differentiation by induction of NF-kappa B.
    Nature. 1989 May 4;339(6219):70-3 PMID: 2654643
  57. Interleukin 1 and cyclic AMP induce kappa immunoglobulin light-chain expression via activation of an NF-kappa B-like DNA-binding protein.
    Mol Cell Biol. 1989 Mar;9(3):959-64 PMID: 2542770
  58. Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor.
    Nature. 1985 Feb 28-Mar 6;313(6005):803-6 PMID: 3883195
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.10.2.561-568.1990
Published
1990-02-00
Pages
561-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360838
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.10.2.561-568.1990 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2