Mitochondrial-Derived Oxidants and Quartz Activation of Chemokine Gene Expression

  • Kevin E. Driscoll
  • Brian W. Howard
  • Janet M. Carter
  • Yvonne M. W. Janssen
  • Brooke T. Mossman
  • Robert J. Isfort
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 500)

Abstract

Macrophage inflammatory protein 2 (MIP-2) is a chemotactic cytokine which mediates neutrophil recruitment in the lung and other tissues. Pneumotoxic particles such as quartz increase MIP-2 expression in rat lung and rat alveolar type II epithelial cells. Deletion mutant analysis of the rat MIP-2 promoter demonstrated quartz-induction depended on a single NFκB consensus binding site. Quartz activation of NFκB and MIP-2 gene expression in RLE-6TN cells was inhibited by anti-oxidants suggesting the responses were dependent on oxidative stress. Consistent with anti-oxidant effects, quartz was demonstrated to increase RLE-6TN cell production of hydrogen peroxide. Rotenone treatment of RLE-6TN cells attenuated hydrogen peroxide production, NFκB activation and MIP-2 gene expression induced by quartz indicating that mitochondria-derived oxidants were contributing to these responses. Collectively, these findings indicate that quartz and crocidolite induction of MIP-2 gene expression in rat alveolar type II cells results from stimulation of an intracellular signaling pathway involving increased generation of hydrogen peroxide by mitochondria and subsequent activation of NFκB.

Key words

chemokines quartz nuclear factor k B mitochondria oxidative stress macrophage inflammatory protein 

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References

  1. De Martin R.B. Vanhove, Q. Cheng, E. Hofer, V. Csizmadia, H. Winkler, and F.H. Bach, 1993. Cytokine-inducible expression in endothelial cells of an IkB-a-like gene is regulated by NFκB. EMBO J. 12 2773–2779.PubMedGoogle Scholar
  2. Driscoll, K.E., D.G. Hassenbein, J.M. Carter, J. Poynter, T.N. Asquith, R.A. Grant, J. Whitten, M.P. Purdon, and R. Takigiku. 1993a. Macrophage inflammatory proteins 1 and 2: expression by rat alveolar macrophages, fibroblasts, and epithelial cells and in rat lung after mineral dust exposure. Am. Rev. Resp. Cell Mol. Biol., 8:311–318.Google Scholar
  3. Driscoll, K.E., D.G. Hassenbein, J.M. Carter, J. Poynter, T.N. Asquith, R.A. Grant, J. Whitten, M.P. Purdon, and R. Takigiku. 1993b. Macrophage inflammatory proteins 1 and 2: expression by rat alveolar macrophages, fibroblasts, and epithelial cells and in rat lung after mineral dust exposure. Am. Rev. Resp. Cell Mol. Biol., 8:311–318.Google Scholar
  4. Driscoll, K.E., D.G. Hassenbein, B.W. Howard, R.J. Isfort, D. Cody, M.H. Tindal, and J.M. Carter, 1995a. Cloning, expression, and functional characterization of rat macrophage inflammatory protein 2: a neutrophil chemoattractant and epithelial cell mitogen. J. Leuk. Biol. 58:359–364.Google Scholar
  5. Driscoll, K.E., P.T. Iype, H.L. Kumari, J.M. Carter, M.J. Aardema, L.L Crosby, M.H. Chestnut, and R.A. LeBoeuf. 1995b. Establishment of immortalized alveolar type ii cell lines from adult rat lungs. In Vitro Cell Develop. Biol.31: 516–527.Google Scholar
  6. Driscoll, K.E., B.W. Howard, J.M. Carter, T.A. Asquith, P. Detilleux, C. Johnston, S.L. Kunkel, D. Paugh, and R.J. Isfort, 1996. Chemokine expression by rat lung epithelial cells: effects of in vitro and in vivo mineral dust exposure. Am. J. Pathol. 149: 1627–1637, 1996.PubMedGoogle Scholar
  7. Forman, H.J. and A Boveris. Superoxide radical and hydrogen peroxide in mitochondria. In: Free Radicals in Biology, New York, Academic Press, 1982, pp 65–90.Google Scholar
  8. Fort, P., L. Marty, L. Piechaczyk, S.E. Sabrouty, C. Dani, P. Jeanteur, P., and J.M. Blanchard. 1985. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate dehydrogenase multigenic family. Nuclei Acid Res. 13:1431–42.CrossRefGoogle Scholar
  9. Frevert, C.W., A. Farone, H. Danaee, J.D. Paulauskis and L. Kobzik. 1995. Functional characterization of rat chemokine macrophage inflammatory protein 2. Inflammation 19:133–142.PubMedCrossRefGoogle Scholar
  10. Greenberger, M.J.R., R.M. Strieter, S.L. Kunkel, J.M. Danforth, L.L. Laichalk, D.C. McGillicuddy, and T.J. Standiford. 1996. Neutralization of macrophage inflammatory protein 2 attenuates neutrophil recruitment and bacterial clearance in murine Kelsiella pneumonia. J. Infect. Dis. 173:159–165.PubMedCrossRefGoogle Scholar
  11. Kamp DW, P. Graceffa, W.A. Pryor and S.A. Weitzman. 1992. The role of free radicals in asbestos-induced diseases. Free Radical Biol Med 12:293–315.CrossRefGoogle Scholar
  12. Pick, E, and D. Mizel. 1981. Rapid assays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J. Immunol Meth. 46:211–226.CrossRefGoogle Scholar
  13. Siebenlist, U., G. Franzoso, and K. Brown. 1994. Structure, regulation and function of NFκB. Annu. Rev. Cell Biol. 10: 705–16.CrossRefGoogle Scholar
  14. Schreck, R., K. Albermann, and P.A. Baeuerle. 1992. Nuclear factor kB: an oxidant stress-responsive transcription factor of eukaryotoc cells. Free Rad. Res. Comm 17:221–237.Google Scholar
  15. Schulze-Osthoff, K., A.C. Bakker, B. Vanhaesebroeck, R. Beyaert, W.A. Jacob, and W. Fiers. 1992. Cytotoxic activity of tumor necrosis factor is mediatd by early damage of mitochondrial functions. J. Biol. Chem. 267: 5317–5323.PubMedGoogle Scholar
  16. Staal, F.J.T., M. Roederer, L.A. Hersenberg, and L.A. Herzenberg, 1990. Intracellular thiols regulate activation of nuclear factor NF-kB and transcription of human immunodeficiency virus. Proc. Natl. Acad. Sci. 87: 9943–9947.PubMedCrossRefGoogle Scholar
  17. Turrens, J.F., A. Alexandre, and A.L. Lehninger. 1985. Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch. Biochem. Biophys. 237:408–411.Google Scholar
  18. Widmer, U., K.R. Manoque, A. Cerami, and B. Sherry, 1993. Genomic Cloning of Promoter Analysis of Macrophage Inflammatory Protein (MIP)-2, MIP-1 α, and MIP1 β, Members of the Chemokine Superfamily of Proinflammatory Cytokines J. Immunol. 150:4996–5012.PubMedGoogle Scholar
  19. Xing, Z., M. Jordana, H. Kirpalani, K.E. Driscoll, T.J. Schall, and J. Gauldie. 1994. Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor, macrophage inflammatory protein-2, interleukin 1 and interleukin-6, but not RANTES or transforming growth factor b, mRNA expression in acute lung inflammation. Am. J. Mol. Cell Biol. 10:148–153.Google Scholar
  20. Zar, J.H. Biostatistical Analysis. 2nd ed. Englewood Cliffs; Prentice-Hall; 1984.Google Scholar
  21. Zhao, Q., L. Simpson, K.E. Driscoll, and G.D. Leikauf. 1998. Chemokine regulation of ozone-induced neutrophil and monocyte inflammation. Am. J. Physiol. Lung Cell Mol Biol. 274:L39–L46.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Kevin E. Driscoll
    • 1
  • Brian W. Howard
    • 1
  • Janet M. Carter
    • 1
  • Yvonne M. W. Janssen
    • 2
  • Brooke T. Mossman
    • 2
  • Robert J. Isfort
    • 1
  1. 1.Procter & Gamble Pharmaceuticals Health Care Research CenterMasonUSA
  2. 2.Department of PathologyUniversity of VermontBurlingtonUSA

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