Institute of Pharmacology, Medical School Hannover, Germany
Correspondence: Dr. Michael Kracht, Institute of Pharmacology, Medical School Hannover, Carl-Neuberg Strasse 1, D-30625 Hannover, Germany. E-mail: Kracht.Michael{at}MH-Hannover.de
Interleukin (IL)-8, a prototypic human chemokine, was detected more than a decade ago as the founding member of the chemokine superfamily. One of the most remarkable properties of IL-8 is the variation of its expression levels. In healthy tissues, IL-8 is barely detectable, but it is rapidly induced by ten- to 100-fold in response to proinflammatory cytokines such as tumor necrosis factor or IL-1, bacterial or viral products, and cellular stress. Recently, significant advances in the understanding of signaling pathways, which coordinately regulate IL-8 transcription as well as mRNA stabilization in response to external stimuli, have been made. Maximal IL-8 amounts are generated by a combination of three different mechanisms: first, derepression of the gene promoter; second, transcriptional activation of the gene by nuclear factor-
B and JUN-N-terminal protein kinase pathways; and third, stabilization of the mRNA by the p38 mitogen-activated protein kinase pathway. In that way, cells are able to rapidly increase and at the same time, to fine-tune the amount of IL-8 secreted and thereby control the extent of leukocytes attracted to sites of tissue injury.
Key Words: MAPK • NF-B • interleukin-8 • transcription • mRNA stability
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J. B. Cowland, T. Muta, and N. Borregaard IL-1beta-Specific Up-Regulation of Neutrophil Gelatinase-Associated Lipocalin Is Controlled by I{kappa}B-{zeta} J. Immunol., May 1, 2006; 176(9): 5559 - 5566. [Abstract] [Full Text] [PDF]
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D. Wang, H. Wang, J. Brown, T. Daikoku, W. Ning, Q. Shi, A. Richmond, R. Strieter, S. K. Dey, and R. N. DuBois CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer J. Exp. Med., April 17, 2006; 203(4): 941 - 951. [Abstract] [Full Text] [PDF]
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E. Adam, K. K. Hansen, O. F. Astudillo, L. Coulon, F. Bex, X. Duhant, E. Jaumotte, M. D. Hollenberg, and A. Jacquet The House Dust Mite Allergen Der p 1, Unlike Der p 3, Stimulates the Expression of Interleukin-8 in Human Airway Epithelial Cells via a Proteinase-activated Receptor-2-independent Mechanism J. Biol. Chem., March 17, 2006; 281(11): 6910 - 6923. [Abstract] [Full Text] [PDF]
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M. Shinkai, G. H. Foster, and B. K. Rubin Macrolide antibiotics modulate ERK phosphorylation and IL-8 and GM-CSF production by human bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L75 - L85. [Abstract] [Full Text] [PDF]
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T. P. Carroll, C. M. Greene, C. C. Taggart, A. G. Bowie, S. J. O'Neill, and N. G. McElvaney Viral Inhibition of IL-1- and Neutrophil Elastase-Induced Inflammatory Responses in Bronchial Epithelial Cells J. Immunol., December 1, 2005; 175(11): 7594 - 7601. [Abstract] [Full Text] [PDF]
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C. L. Medin, K. A. Fitzgerald, and A. L. Rothman Dengue Virus Nonstructural Protein NS5 Induces Interleukin-8 Transcription and Secretion J. Virol., September 1, 2005; 79(17): 11053 - 11061. [Abstract] [Full Text] [PDF]
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J. G. Trevino, J. M. Summy, M. J. Gray, M. B. Nilsson, D. P. Lesslie, C. H. Baker, and G. E. Gallick Expression and Activity of Src Regulate Interleukin-8 Expression in Pancreatic Adenocarcinoma Cells: Implications for Angiogenesis Cancer Res., August 15, 2005; 65(16): 7214 - 7222. [Abstract] [Full Text] [PDF]
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A. Thiefes, S. Wolter, J. F. Mushinski, E. Hoffmann, O. Dittrich-Breiholz, N. Graue, A. Dorrie, H. Schneider, D. Wirth, B. Luckow, et al. Simultaneous Blockade of NF{kappa}B, JNK, and p38 MAPK by a Kinase-inactive Mutant of the Protein Kinase TAK1 Sensitizes Cells to Apoptosis and Affects a Distinct Spectrum of Tumor Necrosis Target Genes J. Biol. Chem., July 29, 2005; 280(30): 27728 - 27741. [Abstract] [Full Text] [PDF]
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E. Y. Fukuda, S. P. Lad, D. P. Mikolon, M. Iacobelli-Martinez, and E. Li Activation of Lipid Metabolism Contributes to Interleukin-8 Production during Chlamydia trachomatis Infection of Cervical Epithelial Cells Infect. Immun., July 1, 2005; 73(7): 4017 - 4024. [Abstract] [Full Text] [PDF]
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P.-L. Yao, Y.-C. Lin, C.-H. Wang, Y.-C. Huang, W.-Y. Liao, S.-S. Wang, J. J. W. Chen, and P.-C. Yang Autocrine and Paracrine Regulation of Interleukin-8 Expression in Lung Cancer Cells Am. J. Respir. Cell Mol. Biol., June 1, 2005; 32(6): 540 - 547. [Abstract] [Full Text] [PDF]
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H.-O. Pae, G.-S. Oh, B.-M. Choi, Y.-M. Kim, and H.-T. Chung A Molecular Cascade Showing Nitric Oxide-Heme Oxygenase-1-Vascular Endothelial Growth Factor-Interleukin-8 Sequence in Human Endothelial Cells Endocrinology, May 1, 2005; 146(5): 2229 - 2238. [Abstract] [Full Text] [PDF]
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E. Hoffmann, A. Thiefes, D. Buhrow, O. Dittrich-Breiholz, H. Schneider, K. Resch, and M. Kracht MEK1-dependent Delayed Expression of Fos-related Antigen-1 Counteracts c-Fos and p65 NF-{kappa}B-mediated Interleukin-8 Transcription in Response to Cytokines or Growth Factors J. Biol. Chem., March 11, 2005; 280(10): 9706 - 9718. [Abstract] [Full Text] [PDF]
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A. J. Ratner, E. S. Lysenko, M. N. Paul, and J. N. Weiser Synergistic proinflammatory responses induced by polymicrobial colonization of epithelial surfaces PNAS, March 1, 2005; 102(9): 3429 - 3434. [Abstract] [Full Text] [PDF]
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L. Guillot, R. Le Goffic, S. Bloch, N. Escriou, S. Akira, M. Chignard, and M. Si-Tahar Involvement of Toll-like Receptor 3 in the Immune Response of Lung Epithelial Cells to Double-stranded RNA and Influenza A Virus J. Biol. Chem., February 18, 2005; 280(7): 5571 - 5580. [Abstract] [Full Text] [PDF]
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H. Buss, A. Dorrie, M. L. Schmitz, E. Hoffmann, K. Resch, and M. Kracht Constitutive and Interleukin-1-inducible Phosphorylation of p65 NF-{kappa}B at Serine 536 Is Mediated by Multiple Protein Kinases Including I{kappa}B Kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF Family Member-associated (TANK)-binding Kinase 1 (TBK1), and an Unknown Kinase and Couples p65 to TATA-binding Protein-associated Factor II31-mediated Interleukin-8 Transcription J. Biol. Chem., December 31, 2004; 279(53): 55633 - 55643. [Abstract] [Full Text] [PDF]
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B. Schmeck, J. Zahlten, K. Moog, V. van Laak, S. Huber, A. C. Hocke, B. Opitz, E. Hoffmann, M. Kracht, J. Zerrahn, et al. Streptococcus pneumoniae-induced p38 MAPK-dependent Phosphorylation of RelA at the Interleukin-8 Promotor J. Biol. Chem., December 17, 2004; 279(51): 53241 - 53247. [Abstract] [Full Text] [PDF]
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Y.-M. Wu, D. R. Robinson, and H.-J. Kung Signal Pathways in Up-regulation of Chemokines by Tyrosine Kinase MER/NYK in Prostate Cancer Cells Cancer Res., October 15, 2004; 64(20): 7311 - 7320. [Abstract] [Full Text] [PDF]
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J. Ovrevik, M. Lag, P. Schwarze, and M. Refsnes p38 and Src-ERK1/2 Pathways Regulate Crystalline Silica-Induced Chemokine Release in Pulmonary Epithelial Cells Toxicol. Sci., October 1, 2004; 81(2): 480 - 490. [Abstract] [Full Text] [PDF]
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M. de Bruin, G. J. Peters, R. Oerlemans, Y. G. Assaraf, A. J. Masterson, A. D. Adema, B. A. C. Dijkmans, H. M. Pinedo, and G. Jansen Sulfasalazine Down-Regulates the Expression of the Angiogenic Factors Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase and Interleukin-8 in Human Monocytic-Macrophage THP1 and U937 Cells Mol. Pharmacol., October 1, 2004; 66(4): 1054 - 1060. [Abstract] [Full Text] [PDF]
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L. Sparkman and V. Boggaram Nitric oxide increases IL-8 gene transcription and mRNA stability to enhance IL-8 gene expression in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L764 - L773. [Abstract] [Full Text] [PDF]
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Q. Si, M.-L. Zhao, A. C. A. Morgan, C. F. Brosnan, and S. C. Lee 15-Deoxy-{Delta}12,14-Prostaglandin J2 Inhibits IFN-Inducible Protein 10/CXC Chemokine Ligand 10 Expression in Human Microglia: Mechanisms and Implications J. Immunol., September 1, 2004; 173(5): 3504 - 3513. [Abstract] [Full Text] [PDF]
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A. Koch, M. Giembycz, R.G. Stirling, S. Lim, I. Adcock, K. Wassermann, E. Erdmann, and K.F. Chung Effect of smoking on MAP kinase-induced modulation of IL-8 in human alveolar macrophages Eur. Respir. J., June 1, 2004; 23(6): 805 - 812. [Abstract] [Full Text] [PDF]
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