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The Journal of Immunology, Vol 153, Issue 1 153-164, Copyright © 1994 by American Association of Immunologists

ARTICLES

Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL-6

C Kunsch, RK Lang, CA Rosen and MF Shannon
Department of Molecular Biology, Human Genome Sciences, Rockville, MD 20850.

Transcriptional activation of the IL-8 gene by several inflammatory mediators, including the cytokines IL-1 and TNF-alpha, is mediated through sequences located between nucleotide -94 and -71 of the IL-8 promoter. Because adjacent binding sites for the inducible transcription factors NF-kappa B and NF-IL-6 are located within this region, we examined the functional interaction of these two transcription factor families in IL-8 gene regulation. Maximal transcriptional activation by PMA in Jurkat T lymphocytes was shown to require intact binding sites for both NF-kappa B and NF-IL-6. Electrophoretic mobility shift analysis indicates that NF-IL-6, as well as other related members of this family, bind specifically to the NF-IL- 6 site in the IL-8 promoter. In addition, NF-kappa B p65 (RelA), but not NF-kappa B p50 (NFKB1), binds specifically to the NF-kappa B site. When incubated together, RelA and NF-IL-6/C/EBP form a ternary complex with this region of the IL-8 promoter; this binding is dependent on intact binding sites for both NF-IL-6 and RelA. Transient cotransfection analyses indicate that the cooperative association of NF- IL-6 and RelA with the IL-8 promoter results in synergistic transcriptional activation. Mutational analyses of RelA demonstrate that the C-terminal transactivation domain and the DNA binding domain are required for synergistic activation with NF-IL-6. In addition, overexpression of the NF-kappa B inhibitor molecule, I kappa B, abolished the RelA- and RelA/NF-IL-6-dependent synergistic activation. These data demonstrate that RelA and members of the C/EBP/NF-IL-6 family can functionally cooperate in transcriptional activation of the IL-8 gene and suggest a common mechanism for inducible regulation of cytokine gene expression.


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N. Mori, K. Oishi, B. Sar, N. Mukaida, T. Nagatake, K. Matsushima, and N. Yamamoto
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Interleukin-6 (IL-6) Production by Astrocytes: Autocrine Regulation by IL-6 and the Soluble IL-6 Receptor
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Central Role of Transcription Factor NF-IL6 for Cytokine and Iron-Mediated Regulation of Murine Inducible Nitric Oxide Synthase Expression
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Regulation of Opioid Receptor Activities
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NF-{kappa}B-Inducing Kinase Is a Common Mediator of IL-17-, TNF-{alpha}-, and IL-1{beta}-Induced Chemokine Promoter Activation in Intestinal Epithelial Cells
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I. Gukovsky, A. S. Gukovskaya, T. A. Blinman, V. Zaninovic, and S. J. Pandol
Early NF-kappa B activation is associated with hormone-induced pancreatitis
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A. Krause, H. Holtmann, S. Eickemeier, R. Winzen, M. Szamel, K. Resch, J. Saklatvala, and M. Kracht
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J. L. Quay, W. Reed, J. Samet, and R. B. Devlin
Air Pollution Particles Induce IL-6 Gene Expression in Human Airway Epithelial Cells via NF-kappa B Activation
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 BloodHome page
P. Oeth, J. Yao, S.-T. Fan, and N. Mackman
Retinoic Acid Selectively Inhibits Lipopolysaccharide Induction of Tissue Factor Gene Expression in Human Monocytes
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M. Ott, J. L. Lovett, L. Mueller, and E. Verdin
Superinduction of IL-8 in T Cells by HIV-1 Tat Protein Is Mediated Through NF-{kappa}B Factors
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 Am. J. Respir. Cell Mol. Bio.Home page
A. B. Carter, M. M. Monick, and G. W. Hunninghake
Lipopolysaccharide-induced NF-kappa B Activation and Cytokine Release in Human Alveolar Macrophages Is PKC-independent and TK- and PC-PLC-dependent
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S. A. Sharma, M. K. R. Tummuru, M. J. Blaser, and L. D. Kerr
Activation of IL-8 Gene Expression by Helicobacter pylori Is Regulated by Transcription Factor Nuclear Factor-{kappa}B in Gastric Epithelial Cells
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K. Knobil, A. M. K. Choi, G. W. Weigand, and D. B. Jacoby
Role of oxidants in influenza virus-induced gene expression
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V. Lakshminarayanan, D. W. A. Beno, R. H. Costa, and K. A. Roebuck
Differential Regulation of Interleukin-8 and Intercellular Adhesion Molecule-1 by H2O2 and Tumor Necrosis Factor-alpha in Endothelial and Epithelial Cells
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 EndocrinologyHome page
T. J. Smith, G. D. Sempowski, C. S. Berenson, H. J. Cao, H.-S. Wang, and R. P. Phipps
Human Thyroid Fibroblasts Exhibit a Distinctive Phenotype in Culture: Characteristic Ganglioside Profile and Functional CD40 Expression
Endocrinology, December 1, 1997; 138(12): 5576 - 5588.
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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
Z. Zhu, W. Tang, J. M. Gwaltney Jr., Y. Wu, and J. A. Elias
Rhinovirus stimulation of interleukin-8 in vivo and in vitro: role of NF-kappa B
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P. Ray, L. Yang, D.-H. Zhang, S. K. Ghosh, and A. Ray
Selective Up-regulation of Cytokine-induced RANTES Gene Expression in Lung Epithelial Cells by Overexpression of Ikappa BR
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T.-a. Imaizumi, K. H. Albertine, D. L. Jicha, T. M. McIntyre, S. M. Prescott, and G. A. Zimmerman
Human Endothelial Cells Synthesize ENA-78: Relationship to IL-8 and to Signaling of PMN Adhesion
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J. J. Breton and M. C. Chabot-Fletcher
The Natural Product Hymenialdisine Inhibits Interleukin-8 Production in U937 Cells by Inhibition of Nuclear Factor-kappa B
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 Arterioscler. Thromb. Vasc. Bio.Home page
P. Oeth, G. C.N. Parry, and N. Mackman
Regulation of the Tissue Factor Gene in Human Monocytic Cells: Role of AP-1, NF-{kappa}B/Rel, and Sp1 Proteins in Uninduced and Lipopolysaccharide-Induced Expression
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G. D. Wu, E. J. Lai, N. Huang, and X. Wen
Oct-1 and CCAAT/Enhancer-binding Protein (C/EBP) Bind to Overlapping Elements within the Interleukin-8 Promoter. THE ROLE OF Oct-1 AS A TRANSCRIPTIONAL REPRESSOR
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H. Harant, R. de Martin, P. J. Andrew, E. Foglar, C. Dittrich, and I. J.D. Lindley
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M. R. Ruocco, X. Chen, C. Ambrosino, E. Dragonetti, W. Liu, M. Mallardo, G. De Falco, C. Palmieri, G. Franzoso, I. Quinto, et al.
Regulation of HIV-1 Long Terminal Repeats by Interaction of C/EBP(NF-IL6) and NF-kappa B/Rel Transcription Factors
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An Activation Function in Pit-1 Required Selectively for Synergistic Transcription
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I. Vietor, I. C. Oliveira, and J. Vilcek
CCAAT Box Enhancer Binding Protein alpha (C/EBP-alpha) Stimulates kappaB Element-mediated Transcription in Transfected Cells
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H.-B. Peng, T. B. Rajavashisth, P. Libby, and J. K. Liao
Nitric Oxide Inhibits Macrophage-Colony Stimulating Factor Gene Transcription in Vascular Endothelial Cells
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Concerted Participation of NF-kappaB and C/EBP Heteromer in Lipopolysaccharide Induction of Serum Amyloid A Gene Expression in Liver
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NF-IL6 (C/EBPbeta ) Vigorously Activates il1b Gene Expression via a Spi-1 (PU.1) Protein-Protein Tether
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M. Komine, L. S. Rao, T. Kaneko, M. Tomic-Canic, K. Tamaki, I. M. Freedberg, and M. Blumenberg
Inflammatory Versus Proliferative Processes in Epidermis. TUMOR NECROSIS FACTOR alpha INDUCES K6b KERATIN SYNTHESIS THROUGH A TRANSCRIPTIONAL COMPLEX CONTAINING NFkappa B AND C/EBPbeta
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H.-M. Hu, Q. Tian, M. Baer, C. J. Spooner, S. C. Williams, P. F. Johnson, and R. C. Schwartz
The C/EBP bZIP Domain Can Mediate Lipopolysaccharide Induction of the Proinflammatory Cytokines Interleukin-6 and Monocyte Chemoattractant Protein-1
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