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EMBO J. Jul 1993; 12(7): 2773–2779.
PMCID: PMC413527

Cytokine-inducible expression in endothelial cells of an I kappa B alpha-like gene is regulated by NF kappa B.

Abstract

The transient expression of many different genes is mediated by the inducible transcription factor p50-p65 NF kappa B, which in turn is regulated by complex formation with its inhibitor I kappa B alpha. We describe here that in porcine aortic endothelial cells, either IL-1 alpha, TNF alpha or LPS upregulates an inhibitor of NF kappa B which we refer to as ECI-6. ECI-6 is by structural and functional criteria an I kappa B alpha protein, the porcine homologue of MAD-3, pp40 and RL/IF-1. We have studied the promoter of the ECI-6/I kappa B alpha gene and provide three lines of evidence that its expression is directly regulated by NF kappa B. First, the 5' regulatory region of ECI-6/I kappa B alpha contains two sites that bind NF kappa B in electrophoretic mobility shift assays. Second, expression following transfection of an ECI-6/I kappa B alpha promoter-luciferase reporter construct is dependent on a co-transfected NF kappa B-p65 subunit. Third, pretreatment of endothelial cells with antioxidants, agents that inhibit activation of NF kappa B, inhibit the expression of ECI-6/I kappa B alpha. We conclude that the regulated expression of ECI-6/I kappa B alpha could represent a novel feedback mechanism by which NF kappa B downregulates its own activity after transient activation of target genes has been achieved.

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  • Auwerx J, Sassone-Corsi P. IP-1: a dominant inhibitor of Fos/Jun whose activity is modulated by phosphorylation. Cell. 1991 Mar 8;64(5):983–993. [PubMed]
  • Baeuerle PA. The inducible transcription activator NF-kappa B: regulation by distinct protein subunits. Biochim Biophys Acta. 1991 Apr 16;1072(1):63–80. [PubMed]
  • Baeuerle PA, Baltimore D. I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988 Oct 28;242(4878):540–546. [PubMed]
  • Baeuerle PA, Lenardo M, Pierce JW, Baltimore D. Phorbol-ester-induced activation of the NF-kappa B transcription factor involves dissociation of an apparently cytoplasmic NF-kappa B/inhibitor complex. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 2):789–798. [PubMed]
  • Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. [PubMed]
  • Bevilacqua MP, Stengelin S, Gimbrone MA, Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. [PubMed]
  • Bussolino F, Breviario F, Tetta C, Aglietta M, Mantovani A, Dejana E. Interleukin 1 stimulates platelet-activating factor production in cultured human endothelial cells. J Clin Invest. 1986 Jun;77(6):2027–2033. [PMC free article] [PubMed]
  • Colotta F, Lampugnani MG, Polentarutti N, Dejana E, Mantovani A. Interleukin-1 induces c-fos protooncogene expression in cultured human endothelial cells. Biochem Biophys Res Commun. 1988 May 16;152(3):1104–1110. [PubMed]
  • Davis N, Ghosh S, Simmons DL, Tempst P, Liou HC, Baltimore D, Bose HR., Jr Rel-associated pp40: an inhibitor of the rel family of transcription factors. Science. 1991 Sep 13;253(5025):1268–1271. [PubMed]
  • de Martin R, Strasswimmer J, Philipson L. A new luciferase promoter insertion vector for the analysis of weak transcriptional activities. Gene. 1993 Feb 14;124(1):137–138. [PubMed]
  • de Wet JR, Wood KV, DeLuca M, Helinski DR, Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. [PMC free article] [PubMed]
  • Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. [PMC free article] [PubMed]
  • Foulkes NS, Mellström B, Benusiglio E, Sassone-Corsi P. Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature. 1992 Jan 2;355(6355):80–84. [PubMed]
  • Ghersa P, Hooft van Huijsduijnen R, Whelan J, DeLamarter JF. Labile proteins play a dual role in the control of endothelial leukocyte adhesion molecule-1 (ELAM-1) gene regulation. J Biol Chem. 1992 Sep 25;267(27):19226–19232. [PubMed]
  • Ghosh S, Baltimore D. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature. 1990 Apr 12;344(6267):678–682. [PubMed]
  • Haskill S, Beg AA, Tompkins SM, Morris JS, Yurochko AD, Sampson-Johannes A, Mondal K, Ralph P, Baldwin AS., Jr Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity. Cell. 1991 Jun 28;65(7):1281–1289. [PubMed]
  • Henkel T, Zabel U, van Zee K, Müller JM, Fanning E, Baeuerle PA. Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-kappa B subunit. Cell. 1992 Mar 20;68(6):1121–1133. [PubMed]
  • Kieran M, Blank V, Logeat F, Vandekerckhove J, Lottspeich F, Le Bail O, Urban MB, Kourilsky P, Baeuerle PA, Israël A. The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. Cell. 1990 Sep 7;62(5):1007–1018. [PubMed]
  • Kovary K, Bravo R. Existence of different Fos/Jun complexes during the G0-to-G1 transition and during exponential growth in mouse fibroblasts: differential role of Fos proteins. Mol Cell Biol. 1992 Nov;12(11):5015–5023. [PMC free article] [PubMed]
  • Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. [PMC free article] [PubMed]
  • Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR. TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem. 1991 Jul 15;266(20):12866–12872. [PubMed]
  • Lenardo M, Pierce JW, Baltimore D. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science. 1987 Jun 19;236(4808):1573–1577. [PubMed]
  • Lindley I, Aschauer H, Seifert JM, Lam C, Brunowsky W, Kownatzki E, Thelen M, Peveri P, Dewald B, von Tscharner V, et al. Synthesis and expression in Escherichia coli of the gene encoding monocyte-derived neutrophil-activating factor: biological equivalence between natural and recombinant neutrophil-activating factor. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9199–9203. [PMC free article] [PubMed]
  • Locksley RM, Heinzel FP, Shepard HM, Agosti J, Eessalu TE, Aggarwal BB, Harlan JM. Tumor necrosis factors alpha and beta differ in their capacities to generate interleukin 1 release from human endothelial cells. J Immunol. 1987 Sep 15;139(6):1891–1895. [PubMed]
  • Lux SE, John KM, Bennett V. Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins. Nature. 1990 Mar 1;344(6261):36–42. [PubMed]
  • Nawroth PP, Handley DA, Esmon CT, Stern DM. Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci U S A. 1986 May;83(10):3460–3464. [PMC free article] [PubMed]
  • Nolan GP, Ghosh S, Liou HC, Tempst P, Baltimore D. DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a rel-related polypeptide. Cell. 1991 Mar 8;64(5):961–969. [PubMed]
  • Opipari AW, Jr, Boguski MS, Dixit VM. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. J Biol Chem. 1990 Sep 5;265(25):14705–14708. [PubMed]
  • Polte T, Newman W, Gopal TV. Full length vascular cell adhesion molecule 1 (VCAM-1). Nucleic Acids Res. 1990 Oct 11;18(19):5901–5901. [PMC free article] [PubMed]
  • Richmond A, Balentien E, Thomas HG, Flaggs G, Barton DE, Spiess J, Bordoni R, Francke U, Derynck R. Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin. EMBO J. 1988 Jul;7(7):2025–2033. [PMC free article] [PubMed]
  • Rogers S, Wells R, Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. [PubMed]
  • Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Mar 22;251(5000):1490–1493. [PubMed]
  • Sasaki M, Kato S, Kohno K, Martin GR, Yamada Y. Sequence of the cDNA encoding the laminin B1 chain reveals a multidomain protein containing cysteine-rich repeats. Proc Natl Acad Sci U S A. 1987 Feb;84(4):935–939. [PMC free article] [PubMed]
  • Schreck R, Meier B, Männel DN, Dröge W, Baeuerle PA. Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J Exp Med. 1992 May 1;175(5):1181–1194. [PMC free article] [PubMed]
  • Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, Krensky AM. A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988 Aug 1;141(3):1018–1025. [PubMed]
  • Shaw G, Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. [PubMed]
  • Simmons D, Makgoba MW, 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. [PubMed]
  • Sironi M, Breviario F, Proserpio P, Biondi A, Vecchi A, Van Damme J, Dejana E, Mantovani A. IL-1 stimulates IL-6 production in endothelial cells. J Immunol. 1989 Jan 15;142(2):549–553. [PubMed]
  • Tewari M, Dobrzanski P, Mohn KL, Cressman DE, Hsu JC, Bravo R, Taub R. Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex. Mol Cell Biol. 1992 Jun;12(6):2898–2908. [PMC free article] [PubMed]
  • Treacy MN, He X, Rosenfeld MG. I-POU: a POU-domain protein that inhibits neuron-specific gene activation. Nature. 1991 Apr 18;350(6319):577–584. [PubMed]
  • Zabel U, Baeuerle PA. Purified human I kappa B can rapidly dissociate the complex of the NF-kappa B transcription factor with its cognate DNA. Cell. 1990 Apr 20;61(2):255–265. [PubMed]
  • Zabel U, Henkel T, Silva MS, Baeuerle PA. Nuclear uptake control of NF-kappa B by MAD-3, an I kappa B protein present in the nucleus. EMBO J. 1993 Jan;12(1):201–211. [PMC free article] [PubMed]
  • Zipfel PF, Irving SG, Kelly K, Siebenlist U. Complexity of the primary genetic response to mitogenic activation of human T cells. Mol Cell Biol. 1989 Mar;9(3):1041–1048. [PMC free article] [PubMed]

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