Role of Oxidants in NF-κB Activation and TNF-α Gene Transcription Induced by Hypoxia and Endotoxin
Tóm tắt
The transcription factor NF-κB stimulates the transcription of proinflammatory cytokines including TNF-α. LPS (endotoxin) and hypoxia both induce NF-κB activation and TNF-α gene transcription. Furthermore, hypoxia augments LPS induction of TNF-α mRNA. Previous reports have indicated that antioxidants abolish NF-κB activation in response to LPS or hypoxia, which suggests that reactive oxygen species (ROS) are involved in NF-κB activation. This study tested whether mitochondrial ROS are required for both NF-κB activation and the increase in TNF-α mRNA levels during hypoxia and LPS. Our results indicate that hypoxia (1.5% O2) stimulates NF-κB and TNF-α gene transcription and increases ROS generation as measured by the oxidant sensitive dye 2′,7′-dichlorofluorescein diacetate in murine macrophage J774.1 cells. The antioxidants N-acetylcysteine and pyrrolidinedithiocarbamic acid abolished the hypoxic activation of NF-κB, TNF-α gene transcription, and increases in ROS levels. Rotenone, an inhibitor of mitochondrial complex I, abolished the increase in ROS signal, the activation of NF-κB, and TNF-α gene transcription during hypoxia. LPS stimulated NF-κB and TNF-α gene transcription but not ROS generation in J774.1 cells. Rotenone, pyrrolidinedithiocarbamic acid, and N-acetylcysteine had no effect on the LPS stimulation of NF-κB and TNF-α gene transcription, indicating that LPS activates NF-κB and TNF-α gene transcription through a ROS-independent mechanism. These results indicate that mitochondrial ROS are required for the hypoxic activation of NF-κB and TNF-α gene transcription, but not for the LPS activation of NF-κB.
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Bone, R. C., R. A. Balk, F. B. Cerra, R. P. Dellinger, A. M. Fein, W. A. Knaus, R. M. Schein, W. J. Sibbald. 1992. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 101: 1644
Beal, A. L., F. B. Cerra. 1994. Multiple organ failure syndrome in the 1990s: systemic inflammatory response and organ dysfunction. JAMA 271: 226
Natanson, C., R. L. Danner, R. J. Elin, J. M. Hosseini, K.W. Peart, S. M. Banks, T. J. MacVittie, R. I. Walker, J. E. Parrillo. 1989. Role of endotoxemia in cardiovascular dysfunction and mortality: Escherichia coli and Staphylococcus aureus challenges in a canine model of human septic shock. J. Clin. Invest. 83: 243
Wright, S. D., R. A. Ramos, P. S. Tobias, R. J. Ulevitch, J. C. Mathison. 1990. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249: 1431
Gallay, P., D. Heumann, D. Le Roy, C. Barras, M. P. Glauser. 1994. Mode of action of anti-lipopolysaccharide-binding protein antibodies for prevention of endotoxemic shock in mice. Proc. Natl. Acad. Sci. USA 91: 7922
Goeddel, D. V.. 1999. Signal transduction by tumor necrosis factor: the Parker B. Francis Lectureship. Chest 116: 69
Natanson, C., P. W. Eichenholz, R. L. Danner, P. Q. Eichacker, W. D. Hoffman, G. C. Kuo, S. M. Banks, T. J. MacVittie, J. E. Parrillo. 1989. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J. Exp. Med. 169: 823
Marino, M. W., A. Dunn, D. Grail, M. Inglese, Y. Noguchi, E. Richards, A. Jungbluth, H. Wada, M. Moore, B. Williamson, S. Basu, L. J. Old. 1997. Characterization of tumor necrosis factor-deficient mice. Proc. Natl. Acad. Sci. USA 94: 8093
Barnes, P. J., M. Karin. 1997. Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 336: 1066
Ghezzi, P., C. A. Dinarello, M. Bianchi, M. E. Rosandich, J. E. Repine, C. W. White. 1991. Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells. Cytokine 3: 189
West, M. A., C. Wilson. 1996. Hypoxic alterations in cellular signal transduction in shock and sepsis. New Horiz. 4: 168
Hempel, S. L., M. M. Monick, G. W. Hunninghake. 1996. Effect of hypoxia on release of IL-1 and TNFα by human alveolar macrophages. Am. J. Respir. Cell Mol. Biol. 14: 170
Ghosh, S., M. J. May, E. B. Kopp. 1998. NF-B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16: 225
Leeper-Woodford, S. K., K. Detmer. 1999. Acute hypoxia increases alveolar macrophage tumor necrosis factor activity and alters NF-κB expression. Am. J. Physiol. 276: L909
Koong, A. C., E. Y. Chen, A. J. Giaccia. 1994. Hypoxia causes the activation of nuclear factor κB through the phosphorylation of IκBα on tyrosine residues. Cancer Res. 54: 1425
Matsui, H., Y. Ihara, Y. Fujio, K. Kunisada, S. Akira, T. Kishimoto, K. Yamauchi-Takihara. 1999. Induction of interleukin (IL)-6 by hypoxia is mediated by nuclear factor (NF)-κB and NF-IL6 in cardiac myocytes. Cardiovasc. Res. 42: 104
Gozal, E., N. Simakajornboon, D. Gozal. 1998. NF-κB induction during in vivo hypoxia in dorsocaudal brain stem of rat: effect of MK-801 and L-NAME. J. Appl. Physiol. 85: 372
Taylor, C. T., N. Fueki, A. Agah, R. M. Hershberg, S. P. Colgan. 1999. Critical role of cAMP response element binding protein expression in hypoxia-elicited induction of epithelial tumor necrosis factor-α. J. Biol. Chem. 274: 19447
Verma, I. M., J. K. Stevenson, E. M. Schwarz, D. Van Antwerp, S. Miyamoto. 1995. Rel/NF-κB/IκB family: intimate tales of association and dissociation. Genes Dev. 9: 2723
Schreck, R., P. Rieber, P. A. Baeuerle. 1991. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-κB transcription factor and HIV-1. EMBO J. 10: 2247
Sen, C. K., L. Packer. 1996. Antioxidant and redox regulation of gene transcription. FASEB J. 10: 709
Muraoka, K., K. Shimizu, X. Sun, Y. K. Zhang, T. Tani, T. Hashimoto, M. Yagi, I. Miyazaki, K. Yamamoto. 1997. Hypoxia, but not reoxygenation, induces interleukin 6 gene expression through NF-κB activation. Transplantation 63: 466
Ginn-Pease, M. E., R. L. Whisler. 1998. Redox signals and NF-κB activation in T cells. Free Radic. Biol. Med. 25: 346
Chandel, N. S., E. Maltepe, E. Goldwasser, C. E. Mathieu, M. C. Simon, P. T. Schumacker. 1998. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc. Natl. Acad. Sci. USA 95: 11715
Zabel, U., R. Schreck, P. A. Baeuerle. 1991. DNA binding of purified transcription factor NF-κB Affinity, specificity, Zn2+ dependence, and differential half-site recognition. J. Biol. Chem. 266252..
Fransen, L., R. Mueller, A. Marmenout, J. Tavernier, J. Van der Heyden, E. Kawashima, A. Chollet, R. Tizard, H. van Heuverswyn, A. van Vliet, M. R. Ruysschaert, W. Fiers. 1985. Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression. Nucleic Acids Res. 13: 4417
Bass, D. A., J. W. Parce, L. R. Dechatelet, P. Szejda, M. C. Seeds, M. Thomas. 1983. J. Immunol. 130: 1910
Tiku, M. L., J. B. Liesch, F. M. Robertson. 1990. Production of hydrogen peroxide by rabbit articular chondrocytes. Enhancement by cytokines. J. Immunol. 145: 690
Li, Y., M. A. Trush. 1998. Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production. Biochem. Biophys. Res. Commun. 253: 295
Majander, A., M. Finel, M. Wikstrom. 1994. Diphenyleneiodonium inhibits reduction of iron-sulfur clusters in the mitochondrial NADH-ubiquinone oxidoreductase (complex I). J. Biol. Chem. 269: 21037
Carter, W. O., P. K. Narayanan, J. P. Robinson. 1994. Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells. J. Leukocyte Biol. 55: 253
Schreck, R., B. Meier, D. N. Mannel, W. Droge, P. A. Baeuerle. 1992. Dithiocarbamates as potent inhibitors of nuclear factor κB activation in intact cells. J. Exp. Med. 175: 1181
Ziegler-Heitbrock, H. W., T. Sternsdorf, J. Liese, B. Belohradsky, C. Weber, A. Wedel, R. Schreck, P. A. Bauerle, M. Strobel. 1993. Pyrrolidine dithiocarbamate inhibits NF-κB mobilization and TNFα production in human monocytes. J. Immunol. 151: 6986
Muller, J. M., H. W. Ziegler-Heitbrock, P. A. Baeuerle. 1993. Nuclear factor κB, a mediator of lipopolysaccharide effects. Immunobiology 187: 233
Han, J., J. D. Lee, L. Bibbs, R. J. Ulevitch. 1994. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265: 808
Schreck, R., K. Albermann, P. A. Baeuerle. 1992. Nuclear factor κB: an oxidative stress-responsive transcription factor of eukaryotic cells. Free Radic. Res. Commun. 17: 221
Meyer, M., R. Schreck, P. A. Baeuerle. 1993. H2O2 and antioxidants have opposite effects on activation of NF-κB and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. EMBO J. 12: 2005
Blackwell, T. S., T. R. Blackwell, E. P. Holden, B. W. Christman, J. W. Christman. 1996. In vivo antioxidant treatment suppresses nuclear factor-κB activation and neutrophilic lung inflammation. J. Immunol. 157: 1630
Suter, P. M., G. Domenighetti, M. D. Schaller, M. C. Laverriere, R. Ritz, C. Perret. 1994. N-Acetylcysteine enhances recovery from acute lung injury in man: a randomized, double-blind, placebo-controlled clinical study. Chest 105: 190
Jepsen, S., P. Herlevsen, P. Knudsen, M. I. Bud, N. O. Klausen. 1992. Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo-controlled study. Crit. Care Med. 20: 918
Camhi, S. L., J. Alam, G. W. Wiegand, B. Y. Chin, A. M. Choi. 1998. Transcriptional activation of the HO-1 gene by lipopolysaccharide is mediated by 5′ distal enhancers: role of reactive oxygen intermediates and AP-1. Am. J. Respir. Cell Mol. Biol. 18: 226