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Inflammatory Cytokines and Lung Toxicity

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Cytokines in Human Health

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Exposure to airborne particles and gases including silica, asbestos, diesel exhaust, and ozone is associated with significant risk of pulmonary and cardiovascular morbidity and mortality. Increasing evidence suggests that macrophages and inflammatory mediators released, including cytokines, play a role in the pathogenic process. In response to lung injury, alveolar macrophages become activated and release increased quantities of cytokines such as TNF-α, IL-1, IL-6, and IL-10, as well as chemokines and growth factors such as TGF-β and PDGF. Although these mediators are released to protect the host and initiate wound repair, when generated in excessive amounts or at inappropriate times or places, they can damage host tissue and exacerbate or perpetuate injury. In this chapter, the role of inflammatory cytokines and growth factors released by macrophages in xenobiotic-induced pulmonary toxicity is reviewed. Potential mechanisms mediating expression of cytokine genes and the implications to human health are also discussed.

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References

  1. Cross CE, Halliwell B. Biological consequences of general environmental contaminants. In: Crystal RG, West JB, eds. The Lung: Scientific foundations, Ed. New York: 1991, pp. 1961–1973.

    Google Scholar 

  2. Lippman M, Yeates DB, Albert RE. Deposition, retention and clearance of inhaled particles. Br J Ind Med 1980;37:337–362.

    Google Scholar 

  3. Laskin DL, Laskin JD. Macrophages, Inflammatory Mediators, and Lung Injury. Methods 1996; 10:61–70.

    CAS  PubMed  Google Scholar 

  4. Laskin DL, Gardner CR, Gerecke DR, Laskin JD. Ozone-induced lung injury: role of macrophages and inflammatory mediators. In: Vallyathan V, Shi X, Castranova V, eds. Reactive Oxygen/Nitrogen Species: Lung Injury and Disease, Ed. New York: 2004, pp. 289–316.

    Google Scholar 

  5. Laskin DL, Pendino KJ. Macrophages and inflammatory mediators in tissue injury. Annu Rev Pharmacol Toxicol 1995;35:655–677.

    CAS  PubMed  Google Scholar 

  6. Larrick JW, Kunkel SL. The role of tumor necrosis factor and interleukin 1 in the immunoinflammatory response. Pharm Res 1988;5:129–139.

    CAS  PubMed  Google Scholar 

  7. Whicher JT, Evans SW. Cytokines in disease. Clin Chem 1990;36:1269–1281.

    CAS  PubMed  Google Scholar 

  8. Cerami A. Inflammatory cytokines. Clin Immunol Immunopathol 1992;62: S3–S10.

    CAS  PubMed  Google Scholar 

  9. Zhang P, Summer WR, Bagby GJ, Nelson S. Innate immunity and pulmonary host defense. Immunol Rev 2000; 173:39–51.

    CAS  PubMed  Google Scholar 

  10. Pathania V, Syal N, Pathak CM, Khanduja KL. Vitamin E suppresses the induction of reactive oxygen species release by lipopolysaccharide, interleukin-lbeta and tumor necrosis factor-alpha in rat alveolar macrophages. J Nutr Sci Vitaminol (Tokyo) 1999;45:675–686.

    CAS  Google Scholar 

  11. Lavnikova N, Drapier JC, Laskin DL. A single exogenous stimulus activates resident rat macrophages for nitric oxide production and tumor cytotoxicity. J Leukoc Biol 1993;54:322–328.

    CAS  PubMed  Google Scholar 

  12. Larrick JW, Wright SC. Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J 1990;4:3215–3223.

    CAS  PubMed  Google Scholar 

  13. Hirano S. Nitric oxide-mediated cytotoxic effects of alveolar macrophages on transformed lung epithelial cells are independent of the beta 2 integrin-mediated intercellular adhesion. Immunology 1998;93:102–108.

    CAS  PubMed  Google Scholar 

  14. Srivastava KD, Rom WN, Jagirdar J, Yie TA, Gordon T, Tchou-Wong KM. Crucial role of interleukinlbeta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice. Am J Respir Crit Care Med 2002; 165: 527–533.

    PubMed  Google Scholar 

  15. Kips JC, Tavernier J, Pauwels RA. Tumor necrosis factor causes bronchial hyperresponsiveness in rats. Am Rev Respir Dis 1992; 145:332–336.

    CAS  PubMed  Google Scholar 

  16. Ohkawara Y, Yamauchi K, Tanno Y, et al. Human lung mast cells and pulmonary macrophages produce tumor necrosis factor-alpha in sensitized lung tissue after IgE receptor triggering. Am J Respir Cell Mol Biol 1992;7:385–392.

    CAS  PubMed  Google Scholar 

  17. Schmitz N, Kurrer M, Kopf M. The IL-1 receptor 1 is critical for Th2 cell type airway immune responses in a mild but not in a more severe asthma model. Eur J Immunol 2003;33:991–1000.

    CAS  PubMed  Google Scholar 

  18. Dubaybo BA. Role of tumor necrosis factor-alpha in regulating fibrotic lung repair. Res Commun Mol Pathol Pharmacol 1998;101:69–83.

    CAS  PubMed  Google Scholar 

  19. Sasaki M, Kashima M, Ito T, et al. Differential regulation of metalloproteinase production, proliferation and chemotaxis of human lung fibroblasts by PDGF, interleukin-lbeta and TNF-alpha. Mediators Inflamm 2000;9:155–160.

    CAS  PubMed  Google Scholar 

  20. Ward PA. Oxygen radicals, cytokines, adhesion molecules, and lung injury. Environ Health Perspect 1994; 102 Suppl 10:13–26.

    CAS  PubMed  Google Scholar 

  21. Ward PA. Role of complement, chemokines, and regulatory cytokines in acute lung injury. Ann N Y Acad Sci 1996;796:104–112.

    CAS  PubMed  Google Scholar 

  22. Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood 1994;83:113–118.

    CAS  PubMed  Google Scholar 

  23. Yu M, Zheng X, Witschi H, Pinkerton KE. The role of interleukin-6 in pulmonary inflammation and injury induced by exposure to environmental air pollutants. Toxicol Sci 2002;68:488–497.

    CAS  PubMed  Google Scholar 

  24. Rollwagen FM, Yu ZY, Li YY, Pacheco ND. IL-6 rescues enterocytes from hemorrhage induced apoptosis in vivo and in vitro by a bcl-2 mediated mechanism. Clin Immunol Immunopathol 1998;89:205–213.

    CAS  PubMed  Google Scholar 

  25. Shingu M, Isayama T, Yasutake C et al. Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation. Inflammation 1994; 18:613–623.

    CAS  PubMed  Google Scholar 

  26. Ulich TR, Yin S, Guo K, Yi ES, Remick D, del Castillo J. Intratracheal injection of endotoxin and cytokines. II. Interleukin-6 and transforming growth factor beta inhibit acute inflammation. Am JPathol 1991;138:1097–1101.

    CAS  Google Scholar 

  27. Ward NS, Waxman AB, Homer RJ et al. Interleukin-6-induced protection in hyperoxic acute lung injury. Am J Respir Cell Mol Biol 2000;22:535–542.

    CAS  PubMed  Google Scholar 

  28. DiCosmo BF, Geba GP, Picarella D et al. Airway epithelial cell expression of interleukin-6 in transgenic mice. Uncoupling of airway inflammation and bronchial hyperreactivity. J Clin Invest 1994;94:2028–2035.

    CAS  PubMed  Google Scholar 

  29. Kuhn C, 3rd, Homer RJ, Zhu Z et al. Airway hyperresponsiveness and airway obstruction in transgenic mice. Morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung. Am J Respir Cell Mol Biol 2000;22: 289–295.

    CAS  PubMed  Google Scholar 

  30. Johnston RA, Schwartzman IN, Flynt L, Shore SA. Role of interleukin-6 in murine airway responses to ozone. Am J Physiol Lung Cell Mol Physiol 2005; 288:L390–L397.

    CAS  PubMed  Google Scholar 

  31. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991;147:3815–3822.

    CAS  PubMed  Google Scholar 

  32. Wang P, Ba ZF, Chaudry IH. Nitric oxide. To block or enhance its production during sepsis? Arch Surg 1994; 129:1137–1142.

    CAS  PubMed  Google Scholar 

  33. Wang P, Wu P, Siegel MI, Egan RW, Billah MM. Interleukin (IL)-IO inhibits nuclear factor kappaB (NF kB) activation in human monocytes. IL-10 and IL-suppress cytokine synthesis by different mechanisms. J Biol Chem 1995;270:9558–9563.

    CAS  PubMed  Google Scholar 

  34. Oberholzer A, Oberholzer C, Moldawer LL. Interleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. Crit Care Med 2002;30:S58–S63.

    CAS  Google Scholar 

  35. Kumar A, Creery WD. The therapeutic potential of interleukin 10 in infection and inflammation. Arch Immunol Ther Exp (Warsz) 2000;48:529–538.

    CAS  Google Scholar 

  36. Opal SM, Huber CE. The role of interleukin-10 in critical illness. Curr Opin Infect Dis 2000;13:221–226.

    CAS  PubMed  Google Scholar 

  37. Mulligan MS, Jones ML, Vaporciyan AA, Howard MC, ard PA. Protective effects of IL-and IL-10 against immune complex-induced lung injury. J Immunol 1993;151:5666–5674.

    CAS  PubMed  Google Scholar 

  38. Bartram U, Speer CP. The role of transforming growth factor beta in lung development and disease. Chest 2004; 125:754–765.

    PubMed  Google Scholar 

  39. Bonner JC. Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev 2004; 15:255–273.

    CAS  PubMed  Google Scholar 

  40. Pendino KJ, Meidhof TM, Heck DE, Laskin JD, Laskin DL. Inhibition of macrophages with gadolinium chloride abrogates ozone-induced pulmonary injury and inflammatory mediator production. Am J Respir Cell Mol Biol 1995;13: 125–132.

    CAS  PubMed  Google Scholar 

  41. Pendino KJ, Shuler RL, Laskin JD, Laskin DL. Enhanced production of interleukin-1, tumor necrosis factor-alpha, and fibronectin by rat lung phagocytes following inhalation of a pulmonary irritant. Am J Respir Cell Mol Biol 1994; 11:279–286.

    CAS  PubMed  Google Scholar 

  42. Ishii Y, Yang H, Sakamoto T et al. Rat alveolar macrophage cytokine production and regulation of neutrophil recruitment following acute ozone exposure. Toxicol Appl Pharmacol 1997; 147:214–223.

    CAS  PubMed  Google Scholar 

  43. Weller BL, Witschi H, Pinkerton KE. Quantitation and localization of pulmonary manganese Superoxide dismutase and tumor necrosis factor alpha following exposure to ozone and nitrogen dioxide. Toxicol Sci 2000;54:452–461.

    CAS  PubMed  Google Scholar 

  44. Johnston CJ, Oberdorster G, Gelein R, Finkelstein JN. Newborn mice differ from adult mice in chemokine and cytokine expression to ozone, but not to endotoxin. Inhal Toxicol 2000; 12:205–224.

    CAS  PubMed  Google Scholar 

  45. Cohen MD, Sisco M, Li Y, Zelikoff JT, Schlesinger RB. Ozone-induced modulation of cell-mediated immune responses in the lungs. Toxicol Appl Pharmacol 2001; 171:71–84.

    CAS  PubMed  Google Scholar 

  46. Bhalla DK, Reinhart PG, Bai C, Gupta SK. Amelioration of ozone-induced lung injury by anti-tumor necrosis factor alpha. Toxicol Sci 2002;69:400–408.

    CAS  PubMed  Google Scholar 

  47. Shore SA, Rivera-Sanchez YM, Schwartzman IN, Johnston RA. Responses to ozone are increased in obese mice. J Appl Physiol 2003;95:938–945.

    CAS  PubMed  Google Scholar 

  48. Fakhrzadeh L, Laskin JD, Gardner CR, Laskin DL. Superoxide dismutaseoverexpressing mice are resistant to ozone-induced tissue injury and increases in nitric oxide and tumor necrosis factor-alpha. Am J Respir Cell Mol Biol 2004;30:280–287.

    CAS  PubMed  Google Scholar 

  49. Fakhrzadeh L, Laskin JD, Laskin DL. Ozone-induced production of nitric oxide and TNF-alpha and tissue injury are dependent on NF-kappaB p50. Am J Physiol Lung Cell Mol Physiol 2004;287:L279–L285.

    CAS  PubMed  Google Scholar 

  50. Park JW, Taube C, Swasey C et al. Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone. Am J Respir Cell Mol Biol 2004;30:830–836.

    CAS  PubMed  Google Scholar 

  51. Young C, Bhalla DK. Effects of ozone on the epithelial and inflammatory responses in the airways: role of tumor necrosis factor. J Toxicol Environ Health 1995;46:329–342.

    CAS  PubMed  Google Scholar 

  52. Pearson AC, Bhalla DK. Effects of ozone on macrophage adhesion in vitro and epithelial and inflammatory responses in vivo: the role of cytokines. J Toxicol Environ Health 1997;50:143–157.

    CAS  PubMed  Google Scholar 

  53. Fakhrzadeh L, Laskin JD, Laskin DL. Deficiency in inducible nitric oxide synthase protects mice from ozone-induced lung inflammation and tissue injury. Am J Respir Cell Mol Biol 2002;26:413–419.

    CAS  PubMed  Google Scholar 

  54. Cho HY, Zhang LY, Kleeberger SR. Ozone-induced lung inflammation and hyperreactivity are mediated via tumor necrosis factor-alpha receptors. Am J Physiol Lung Cell Mol Physiol 2001;280:L537–L546.

    CAS  PubMed  Google Scholar 

  55. Shore SA, Schwartzman IN, Le Blanc B, Murthy GG, Doerschuk CM. Tumor necrosis factor receptor 2 contributes to ozone-induced airway hyperresponsiveness in mice. Am J Respir Crit Care Med 2001; 164:602–607.

    CAS  PubMed  Google Scholar 

  56. Thomas PS, Yates DH, Barnes PJ. Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects. Am J Respir Crit Care Med 1995; 152:76–80.

    CAS  PubMed  Google Scholar 

  57. Wesselius LJ, Smirnov IM, O’Brien-Ladner AR, Nelson ME. Synergism of intratracheally administered tumor necrosis factor with interleukin-1 in the induction of lung edema in rats. J Lab Clin Med 1995;125:618–625.

    CAS  PubMed  Google Scholar 

  58. Koh Y, Hybertson BM, Jepson EK, Repine JE. Tumor necrosis factor induced acute lung leak in rats: less than with interleukin-1. Inflammation 1996;20:461–469.

    CAS  PubMed  Google Scholar 

  59. Dye JA, Madden MC, Richards JH, Lehmann JR, Devlin RB, Costa DL. Ozone effects on airway responsiveness, lung injury, and inflammation. Comparative rat strain and in vivo/in vitro investigations. Inhal Toxicol 1999; 11:1015–1040.

    CAS  PubMed  Google Scholar 

  60. Johnston CJ, Stripp BR, Reynolds SD, Avissar NE, Reed CK, Finkelstein JN. Inflammatory and antioxidant gene expression in C57BL/6J mice after lethal and sublethal ozone exposures. Exp Lung Res 1999;25:81–97.

    CAS  PubMed  Google Scholar 

  61. Johnston CJ, Reed CK, Avissar NE, Gelein R, Finkelstein JN. Antioxidant and inflammatory response after acute nitrogen dioxide and ozone exposures in C57B1/6 mice. Inhal Toxicol 2000; 12:187–203.

    CAS  PubMed  Google Scholar 

  62. Jonsson LM, Edlund T, Marklund SL, Sandstrom T. Increased ozone-induced airway neutrophilic inflammation in extracellular-superoxide dismutase null mice. Respir Med 2002;96:209–214.

    CAS  PubMed  Google Scholar 

  63. Jorres RA, Holz O, Zachgo W et al. The effect of repeated ozone exposures on inflammatory markers in bronchoalveolar lavage fluid and mucosal biopsies. Am J Respir Crit Care Med 2000;161:1855–1861.

    CAS  PubMed  Google Scholar 

  64. Bornholdt J, Dybdahl M, Vogel U, Hansen M, Loft S, Wallin H. Inhalation of ozone induces DNA strand breaks and inflammation in mice. Mutat Res 2002;520:63–71.

    CAS  PubMed  Google Scholar 

  65. Shore SA, Johnston RA, Schwartzman IN, Chism D, Krishna Murthy GG. Ozone-induced airway hyperresponsiveness is reduced in immature mice. J Appl Physiol 2002;92:1019–1028.

    CAS  PubMed  Google Scholar 

  66. Samet JM, Hatch GE, Horstman D et al. Effect of antioxidant supplementation on ozone-induced lung injury in human subjects. Am J Respir Crit Care Med 2001;164:819–825.

    CAS  PubMed  Google Scholar 

  67. Vincent R, Vu D, Hatch G et al. Sensitivity of lungs of aging Fischer 344 rats to ozone: assessment by bronchoalveolar lavage. Am J Physiol Lung Cell Mol Physiol 1996;271:L555–L565.

    CAS  Google Scholar 

  68. Johnston C, Holm B, Finkelstein JN. Differential proinflammatory cytokine responses of the lung to ozone and lipopolysaccharide exposure during postnatal development. Exp Lung Res 2004;30:599–614.

    CAS  Google Scholar 

  69. Bhalla DK, Gupta SK. Lung injury, inflammation, and inflammatory stimuli in rats exposed to ozone. J Toxicol Environ Health 2000;59:211–228.

    CAS  Google Scholar 

  70. Driscoll KE, Simpson L, Carter J, Hassenbein D, Leikauf GD. Ozone inhalation stimulates expression of a neutrophil chemotactic protein, macrophage inflammatory protein 2. Toxicol Appl Pharmacol 1993; 119:306–309.

    CAS  PubMed  Google Scholar 

  71. Zhao Q, Simpson LG, Driscoll KE, Leikauf GD. Chemokine regulation of ozone-induced neutrophil and monocyte inflammation. Am J Physiol Lung Cell Mol Physiol 1998;274:L39–L46.

    CAS  Google Scholar 

  72. Johnston CJ, Oberdorster G, Finkelstein JN. Recovery from oxidant-mediated lung injury: response of metallothionein, MIP-2, and MCP-1 to nitrogen dioxide, oxygen, and ozone exposures. Inhal Toxicol 2001;13:689–702.

    CAS  PubMed  Google Scholar 

  73. Johnston RA, Mizgerd JP, Shore SA. CXCR2 is essential for maximal neutrophil recruitment and methacholine responsiveness after ozone exposure. Am J Physiol Lung Cell Mol Physiol 2005;288:L61–L67.

    CAS  PubMed  Google Scholar 

  74. Michalec L, Choudhury BK, Postlethwait E et al. CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation. J Immunol 2002;168:846–852.

    CAS  PubMed  Google Scholar 

  75. Kenyon NJ, van der Vliet A, Schock BC, Okamoto T, McGrew GM, Last JA. Susceptibility to ozone-induced acute lung injury in iNOS-deficient mice. Am J Physiol Lung Cell Mol Physiol 2002;282:L540–L545.

    CAS  PubMed  Google Scholar 

  76. Park JW, Taube C, Joetham A et al. Complement activation is critical to airway hyperresponsiveness after acute ozone exposure. Am J Respir Crit Care Med 2004; 169:726–732.

    PubMed  Google Scholar 

  77. Haddad EB, Salmon M, Sun J et al. Dexamethasone inhibits ozone-induced gene expression of macrophage inflammatory protein-2 in rat lung. FEBS Lett 1995;363:285–288.

    CAS  PubMed  Google Scholar 

  78. Haddad EB, Salmon M, Koto H, Barnes PJ, Adcock I, Chung KF. Ozone induction of cytokine-induced neutrophil chemoattractant (CINC) and nuclear factor-kappaB in rat lung: inhibition by corticosteroids. FEBS Lett 1996;379:265–268.

    CAS  PubMed  Google Scholar 

  79. Koto H, Salmon M, Haddadel B, Huang TJ, Zagorski J, Chung KF. Role of cytokine-induced neutrophil chemoattractant (CINC) in ozone-induced airway inflammation and hyperresponsiveness. Am J Respir Crit Care Med 1997; 156:234–239.

    CAS  PubMed  Google Scholar 

  80. Reinhart PG, Gupta SK, Bhalla DK. Attenuation of ozone-induced lung injury by interleukin-10. Toxicol Lett 1999; 110:35–42.

    CAS  PubMed  Google Scholar 

  81. Osinubi OY, Gochfeld M, Kipen HM. Health effects of asbestos and nonasbestos fibers. Environ Health Perspect 2000; 108:665–674.

    CAS  PubMed  Google Scholar 

  82. Mossman BT, Churg A. Mechanisms in the pathogenesis of asbestosis and silicosis. Am J Respir Crit Care Med 1998;157:1666–1680.

    CAS  PubMed  Google Scholar 

  83. Castranova V, Vallyathan V. Silicosis and coal workers’ pneumoconiosis. Environ Health Perspect 2000; 108 Suppl 4:675–684.

    CAS  PubMed  Google Scholar 

  84. Castranova V. Signaling pathways controlling the production of inflammatory mediators in response to crystalline silica exposure: role of reactive oxygen/ nitrogen species. Free Radic Biol Med 2004;37:916–925.

    CAS  PubMed  Google Scholar 

  85. Simeonova PP, Luster MI. Asbestos induction of nuclear transcription factors and interleukin 8 gene regulation. Am J Respir Cell Mol Biol 1996; 15:787–795.

    CAS  PubMed  Google Scholar 

  86. Driscoll KE, Carter JM, Hassenbein DG, Howard B. Cytokines and particleinduced inflammatory cell recruitment. Environ Health Perspect 1997; 105 Suppl 5:1159–1164.

    CAS  PubMed  Google Scholar 

  87. Kamp DW, Weitzman SA. The molecular basis of asbestos induced lung injury. Thorax 1999;54:638–652.

    CAS  PubMed  Google Scholar 

  88. Shaw RJ. The role of lung macrophages at the interface between chronic inflammation and fibrosis. Respir Med 1991;85:267–273.

    CAS  PubMed  Google Scholar 

  89. Broser M, Zhang Y, Aston C, Harkin T, Rom WN. Elevated interleukin-8 in the alveolitis of individuals with asbestos exposure. Int Arch Occup Environ Health 1996;68:109–114.

    CAS  PubMed  Google Scholar 

  90. Johnston CJ, Driscoll KE, Finkelstein JN et al. Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica. Toxicol Sci 2000;56:405–413.

    CAS  PubMed  Google Scholar 

  91. Driscoll KE, Guthrie GD. Crystalline silica and silicosis. In: Roth RA, eds. Comprehensive Toxicology, First Ed. New York: Toxicology of the respiratory system, 1997, pp. 373–391.

    Google Scholar 

  92. Yucesoy B, Vallyathan V, Landsittel DP, Simeonova P, Luster MI. Cytokine polymorphisms in silicosis and other pneumoconioses. Mol Cell Biochem 2002;234–235:219–224.

    PubMed  Google Scholar 

  93. Pryhuber GS, Huyck HL, Baggs R, Oberdorster G, Finkelstein JN. Induction of chemokines by low-dose intratracheal silica is reduced in TNFRI (p55) null mice. Toxicol Sci 2003;72:150–157.

    CAS  PubMed  Google Scholar 

  94. Hubbard AK, Timblin CR, Shukla A, Rincon M, Mossman BT. Activation of NF-kappaB-dependent gene expression by silica in lungs of luciferase reporter mice. Am J Physiol Lung Cell Mol Physiol 2002;282:L968–L975.

    CAS  PubMed  Google Scholar 

  95. Desaki M, Sugawara I, Iwakura Y, Yamamoto K, Takizawa H. Role of interferon-gamma in the development of murine bronchus-associated lymphoid tissues induced by silica in vivo. Toxicol Appl Pharmacol 2002; 185:1–7.

    CAS  PubMed  Google Scholar 

  96. Davis GS, Pfeiffer LM, Hemenway DR. Persistent overexpression of interleukin-1 beta and tumor necrosis factor-alpha in murine silicosis. J Environ Pathol Toxicol Oncol 1998; 17:99–114.

    CAS  PubMed  Google Scholar 

  97. Zeidler P, Hubbs A, Battelli L, Castranova V. Role of inducible nitric oxide synthase-derived nitric oxide in silica-induced pulmonary inflammation and fibrosis. J Toxicol Environ Health A 2004;67:1001–1026.

    CAS  PubMed  Google Scholar 

  98. Hata J, Aoki K, Mitsuhashi H, Uno H. Change in location of cytokine-induced neutrophil chemoattractants (CINCs) in pulmonary silicosis. Exp Mol Pathol 2003;75:68–73.

    CAS  PubMed  Google Scholar 

  99. Rao KM, Porter DW, Meighan T, Castranova V. The sources of inflammatory mediators in the lung after silica exposure. Environ Health Perspect 2004; 112:1679–1686.

    CAS  PubMed  Google Scholar 

  100. Yuen IS, Hartsky MA, Snajdr SI, Warheit DB. Time course of chemotactic factor generation and neutrophil recruitment in the lungs of dust-exposed rats. Am J Respir Cell Mol Biol 1996;15:268–274.

    CAS  PubMed  Google Scholar 

  101. Hill GD, Mangum JB, Moss OR, Everitt JI. Soluble ICAM-1, MCP-1, and MIP-2 protein secretion by rat pleural mesothelial cells following exposure to amosite asbestos. Exp Lung Res 2003;29:277–290.

    CAS  PubMed  Google Scholar 

  102. Mascagni P, Corsini E, Pettazzoni M et al. Determination of interleukin-8 in induced sputum of workers exposed to low concentrations of asbestos. G Ital Med Lav Ergon 2003;25 Suppl:137.

    CAS  PubMed  Google Scholar 

  103. Vanhee D, Gosset P, Boitelle A, Wallaert B, Tonnel AB. Cytokines and cytokine network in silicosis and coal workers’ pneumoconiosis. Eur Respir J 1995;8:834–842.

    CAS  PubMed  Google Scholar 

  104. Driscoll KE, Howard BW, Carter JM et al. Alpha-quartz-induced chemokine expression by rat lung epithelial cells: effects of in vivo and in vitro particle exposure. Am J Pathol 1996; 149:1627–1637.

    CAS  PubMed  Google Scholar 

  105. Gossart S, Cambon C, Orfila C et al. Reactive oxygen intermediates as regulators of TNF-alpha production in rat lung inflammation induced by silica. J Immunol 1996;156:1540–1548.

    CAS  PubMed  Google Scholar 

  106. Choe N, Tanaka S, Xia W, Hemenway DR, Roggli VL, Kagan E. Pleural macrophage recruitment and activation in asbestos-induced pleural injury. Environ Health Perspect 1997;105 Suppl 5:1257–1260.

    CAS  PubMed  Google Scholar 

  107. Brass DM, Hoyle GW, Poovey HG, Liu JY, Brody AR. Reduced tumor necrosis factor alpha and transforming growth factor beta 1 expression in the lungs of inbred mice that fail to develop fibroproliferative lesions consequent to asbestos exposure. Am J Pathol 1999;154:853–862.

    CAS  PubMed  Google Scholar 

  108. Ortiz LA, Lasky J, Lungarella G et al. Upregulation of the p75 but not the p55 TNF-alpha receptor mRNA after silica and bleomycin exposure and protection from lung injury in double receptor knockout mice. Am J Respir Cell Mol Biol 1999;20:825–833.

    CAS  PubMed  Google Scholar 

  109. Corsini E, Giani A, Peano S, Marinovich M, Galli CL. Resistance to silicainduced lung fibrosis in senescent rats: role of alveolar macrophages and tumor necrosis factor-alpha (TNF). Mech Ageing Dev 2004; 125:145–146.

    CAS  PubMed  Google Scholar 

  110. Porter DW, Ye J, Ma J et al. Time course of pulmonary response of rats to inhalation of crystalline silica: NF-kappa B activation, inflammation, cytokine production, and damage. Inhal Toxicol 2002; 14:349–367.

    CAS  PubMed  Google Scholar 

  111. Castranova V, Porter D, Millecchia L, Ma JY, Hubbs AF, Teass A. Effect of inhaled crystalline silica in a rat model: time course of pulmonary reactions. Mol Cell Biochem 2002;234-235:177–184.

    PubMed  Google Scholar 

  112. Driscoll KE, Maurer JK, Lindenschmidt RC, Romberger D, Rennard SI, Crosby L. Respiratory tract responses to dust: relationships between dust burden, lung injury, alveolar macrophage fibronectin release, and the development of pulmonary fibrosis. Toxicol Appl Pharmacol 1990;106:88–101.

    CAS  PubMed  Google Scholar 

  113. Driscoll KE, Maurer JK, Higgins J, Poynter J. Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis. J Toxicol Environ Health 1995;46:155–169.

    CAS  PubMed  Google Scholar 

  114. Orfila C, Lepert JC, Gossart S, Frisach MF, Cambon C, Pipy B. Immunocy-tochemical characterization of lung macrophage surface phenotypes and expression of cytokines in acute experimental silicosis in mice. Histochem J 1998;30:857–867.

    CAS  PubMed  Google Scholar 

  115. Zhang Y, Lee TC, Guillemin B, Yu MC, Rom WN. Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure. J Immunol 1993;150:4188–4196.

    CAS  PubMed  Google Scholar 

  116. Huaux F, Arras M, Vink A, Renauld JC, Lison D. Soluble tumor necrosis factor (TNF) receptors p55 and p75 and interleukin-10 downregulate TNF-alpha activity during the lung response to silica particles in NMRI mice. Am J Respir Cell Mol Biol 1999;21:137–145.

    CAS  PubMed  Google Scholar 

  117. Miller MD, Krangel MS. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol 1992; 12: 17–26.

    CAS  PubMed  Google Scholar 

  118. Liu JY, Brody AR. Increased TGF-betal in the lungs of asbestos-exposed rats and mice: reduced expression in TNF-alpha receptor knockout mice. J Environ Pathol Toxicol Oncol 2001;20:97–108.

    CAS  PubMed  Google Scholar 

  119. Driscoll KE, Hassenbein DG, Carter JM, Kunkel SL, Quinlan TR, Mossman BT. TNF alpha and increased chemokine expression in rat lung after particle exposure. Toxicol Lett 1995;82-83:483–489.

    PubMed  Google Scholar 

  120. Piguet PF. Is “tumor necrosis factor” the major effector of pulmonary fibrosis? Eur Cytokine Netw 1990; 1:257–258.

    CAS  PubMed  Google Scholar 

  121. Piguet PF, Collart MA, Grau GE, Sappino AP, Vassalli P. Requirement of tumour necrosis factor for development of silica-induced pulmonary fibrosis. Nature 1990;344:245–247.

    CAS  PubMed  Google Scholar 

  122. Liu JY, Brass DM, Hoyle GW, Brody AR. TNF-alpha receptor knockout mice are protected from the fibroproliferative effects of inhaled asbestos fibers. Am J Pathol 1998;153:1839–1847.

    CAS  PubMed  Google Scholar 

  123. Miyazaki Y, Araki K, Vesin C et al. Expression of a tumor necrosis factor-alpha transgene in murine lung causes lymphocytic and fibrosing alveolitis. A mouse model of progressive pulmonary fibrosis. J Clin Invest 1995;96:250–259.

    CAS  PubMed  Google Scholar 

  124. Simeonova PP, Toriumi W, Kommineni C et al. Molecular regulation of IL-6 activation by asbestos in lung epithelial cells: role of reactive oxygen species. J Immunol 1997;159:3921–3928.

    CAS  PubMed  Google Scholar 

  125. Kline JN, Schwartz DA, Monick MM, Floerchinger CS, Hunninghake GW. Relative release of interleukin-1 beta and interleukin-1 receptor antagonist by alveolar macrophages. A study in asbestos-induced lung disease, sarcoidosis, and idiopathic pulmonary fibrosis. Chest 1993; 104:47–53.

    CAS  PubMed  Google Scholar 

  126. Li XY, Lamb D, Donaldson K. The production of TNF-alpha and IL-1-like activity by bronchoalveolar leucocytes after intratracheal instillation of crocidolite asbestos. Int J Exp Pathol 1993;74:403–404.

    CAS  PubMed  Google Scholar 

  127. Lemaire I, Ouellet S. Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts. J Toxicol Environ Health 1996;47:465–478.

    CAS  PubMed  Google Scholar 

  128. Lindroos PM, Coin PG, Badgett A, Morgan DL, Bonner JC. Alveolar macrophages stimulated with titanium dioxide, chrysotile asbestos, and residual oil fly ash upregulate the PDGF receptor-alpha on lung fibroblasts through an IL-lbeta-dependent mechanism. Am J Respir Cell Mol Biol 1997; 16:283–292.

    CAS  PubMed  Google Scholar 

  129. Huaux F, Louahed J, Hudspith B et al. Role of interleukin-10 in the lung response to silica in mice. Am J Respir Cell Mol Biol 1998;18:51–59.

    CAS  PubMed  Google Scholar 

  130. Barbarin V, Arras M, Misson P et al. Characterization of the effect of interleukin-10 on silica-induced lung fibrosis in mice. Am J Respir Cell Mol Biol 2004;31:78–85.

    CAS  PubMed  Google Scholar 

  131. Driscoll KE, Carter JM, Howard BW et al. Interleukin-10 regulates quartzinduced pulmonary inflammation in rats. Am J Physiol Lung Cell Mol Physiol 1998;275:L887–L894.

    CAS  Google Scholar 

  132. Brody AR, Liu JY, Brass D, Corti M. Analyzing the genes and peptide growth factors expressed in lung cells in vivo consequent to asbestos exposure and in vitro. Environ Health Perspect 1997;105 Suppl 5:1165–1171.

    CAS  PubMed  Google Scholar 

  133. Perdue TD, Brody AR. Distribution of transforming growth factor-betal, fibronectin, and smooth muscle actin in asbestos-induced pulmonary fibrosis in rats. J Histochem Cytochem 1994;42:1061–1070.

    CAS  PubMed  Google Scholar 

  134. Liu JY, Morris GF, Lei WH, Corti M, Brody AR. Up-regulated expression of transforming growth factor-alpha in the bronchiolar-alveolar duct regions of asbestos-exposed rats. Am J Pathol 1996; 149:205–217.

    CAS  PubMed  Google Scholar 

  135. Korfhagen TR, Swantz RJ, Wert SE et al. Respiratory epithelial cell expression of human transforming growth factor-alpha induces lung fibrosis in transgenic mice. J Clin Invest 1994;93:1691–1699.

    CAS  PubMed  Google Scholar 

  136. Sacks M, Gordon J, Bylander J et al. Silica-induced pulmonary inflammation in rats: activation of NF-kappaB and its suppression by dexamethasone. Biochem Biophys Res Commun 1998;253:181–184.

    CAS  PubMed  Google Scholar 

  137. Piguet PF, Rosen H, Vesin C, Grau GE. Effective treatment of the pulmonary fibrosis elicited in mice by bleomycin or silica with anti-CD-11 antibodies. Am Rev Respir Dis 1993;147:435–441.

    CAS  PubMed  Google Scholar 

  138. Piguet PF, Vesin C, Grau GE, Thompson RC. Interleukin 1 receptor antagonist (IL-Ira) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica. Cytokine 1993;5:57–61.

    CAS  PubMed  Google Scholar 

  139. Xie QM, Tang HF, Chen JQ, Bian RL. Pharmacological actions of tetrandrine in inflammatory pulmonary diseases. Acta Pharmacol Sin 2002;23:1107–1113.

    CAS  PubMed  Google Scholar 

  140. Seow WK, Ferrante A, Li SY, Thong YH. Suppression of human monocyte interleukin 1 production by the plant alkaloid tetrandrine. Clin Exp Immunol 1989;75:47–51.

    CAS  PubMed  Google Scholar 

  141. Chang DM, Chang WY, Kuo SY, Chang ML. The effects of traditional antirheumatic herbal medicines on immune response cells. J Rheumatol 1997;24:436–441.

    CAS  PubMed  Google Scholar 

  142. Donaldson K, Gilmour MI, MacNee W. Asthma andPMlO. Respiratory Research 2000;l:12–15.

    Google Scholar 

  143. Pope CA, III, Burnett RT, Thun MJ et al. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 2002;287:1132–1141.

    CAS  PubMed  Google Scholar 

  144. Air quality criteria for particulate matter. U. S. Environmental Protection Agency Research Triangle Park, NC: 2004.

    Google Scholar 

  145. Health assessment document for diesel engine exhaust. U. S. Envirinmental Protection Agency Washington DC: 2002.

    Google Scholar 

  146. Singh P, DeMarini DM, Dick CA et al. Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice. Environ Health Perspect 2004; 112:820–825.

    CAS  PubMed  Google Scholar 

  147. Kongerud J, Madden MC, Hazucha M, Peden D. Nasal responses in asthmatic and nonasthmatic subjects following exposure to diesel exhaust particles. Inhal Toxicol 2006; 18:589–594.

    CAS  PubMed  Google Scholar 

  148. Li N, Wang M, Oberley TD, Sempf JM, Nel AE. Comparison of the prooxidative and proinflammatory effects of organic diesel exhaust particle chemicals in bronchial epithelial cells and macrophages. J Immunol 2002; 169: 4531–4541.

    CAS  PubMed  Google Scholar 

  149. Abe S, Takizawa H, Sugawara I et al. Diesel exhaust (DE)-induced cytokine expression in human bronchial epithelial cells: a study with a new cell exposure system to freshly generated DE in vitro. Am J Resp Cell Mol Biol 2000; 22:296–303.

    CAS  Google Scholar 

  150. Hashimoto S, Gon Y, Takeshita I et al. Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation. Am J Respir Crit Care Med 2000;161:280–285.

    CAS  PubMed  Google Scholar 

  151. Saber AT, Jacobsen NR, Bornholdt J et al. Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor. Part Fibre Toxicol 2006;3:4–11.

    PubMed  Google Scholar 

  152. Inoue K, Takano H, Yanagisawa R et al. The role of toll-like receptor 4 in airway inflammation induced by diesel exhaust particles. Arch Toxicol 2006; 80:275–279.

    CAS  PubMed  Google Scholar 

  153. Rao KM, Ma JY, Meighan T, Barger MW, Pack D, Vallyathan V. Time course of gene expression of inflammatory mediators in rat lung after diesel exhaust particle exposure. Environ Health Perspect 2005;113:612–617.

    CAS  PubMed  Google Scholar 

  154. Nordenhall C, Pourazar J, Blomberg A, Levin JO, Sandstrom T, Adelroth E. Airway inflammation following exposure to diesel exhaust: a study of time kinetics using induced sputum. Eur Respir J 2000;15:1046–1051.

    CAS  PubMed  Google Scholar 

  155. Stenfors N, Nordenhall C, Salvi S S et al. Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel. Eur Respir J 2004;23:82–86.

    CAS  PubMed  Google Scholar 

  156. Ichinose T, Furuyama A, Sagai M. Biological effects of diesel exhaust particles (DEP). II. Acute toxicity of DEP introduced into lung by intratracheal instillation. Toxicology 1995;99:153–167.

    CAS  PubMed  Google Scholar 

  157. Donaldson K, Stone V, Seaton A, MacNee W. Ambient particle inhalation and the cardiovascular system: potential mechanisms. Environ Health Perspect 2001;109 Suppl 4:523–527.

    CAS  PubMed  Google Scholar 

  158. Boland S, Bonvallot V, Fournier T et al. Mechanisms of GM-CSF increase by diesel exhaust particles in human airway epithelial cells. Am J of Physiol Lung Cell Mol Physiol 2000;278:L25–L32.

    CAS  Google Scholar 

  159. Takizawa H, Abe S, Okazaki H et al. Diesel exhaust particles upregulate eotaxin gene expression in human bronchial epithelial cells via nuclear factor-kappaB-dependent pathway. Am J Physiol Lung Cell Mol Physiol 2003; 284:L1055–L1062.

    CAS  PubMed  Google Scholar 

  160. Reed MD, Gigliotti AP, McDonald JD et al. Health effects of subchronic exposure to environmental levels of diesel exhaust. Inhal Toxicol 2004; 16:177–193.

    CAS  PubMed  Google Scholar 

  161. Amakawa K, Terashima T, Matsuzaki T, Matsumaru A, Sagai M, Yamaguchi K. Suppressive effects of diesel exhaust particles on cytokine release from human and murine alveolar macrophages. Exp Lung Res 2003;29:149–164.

    CAS  PubMed  Google Scholar 

  162. Becker S, Mundandhara S, Devlin RB, Madden M. Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies. Toxicol Appl Pharmacol 2005;207:269–275.

    PubMed  Google Scholar 

  163. Pope CA, III. Epidemiology of fine particulate air pollution and human health: biologic mechanisms and who’s at risk?. Environ Health Perspect 2000; 108 Suppl 4:713–723.

    PubMed  Google Scholar 

  164. Castranova V, Ma JY, Yang HM et al. Effect of exposure to diesel exhaust particles on the susceptibility of the lung to infection. Environ Health Perspect 2001;109 Suppl 4:609–612.

    CAS  PubMed  Google Scholar 

  165. Yang HM, Antonini JM, Barger MW et al. Diesel exhaust particles suppress macrophage function and slow the pulmonary clearance of Listeria monocytogenes in rats. Environ Health Perspect 2001;109:515–521.

    CAS  PubMed  Google Scholar 

  166. Harrod KS, Jaramillo RJ, Rosenberger CL et al. Increased susceptibility to RSV infection by exposure to inhaled diesel engine emissions. Am J Resp Cell Mol Biol 2003;28:451–463.

    CAS  Google Scholar 

  167. Takano H, Yanagisawa R, Ichinose T et al. Diesel exhaust particles enhance lung injury related to bacterial endotoxin through expression of proinflammatory cytokines, chemokines, and intercellular adhesion molecule1. Am J Respir Crit Care Med 2002;165:1329–1335.

    PubMed  Google Scholar 

  168. Delfino RJ. Epidemiologic evidence for asthma and exposure to air toxics: linkages between occupational, indoor, and community air pollution research. Environ Health Perspect 2002; 110 Suppl 4:573–589.

    PubMed  Google Scholar 

  169. Diaz-Sanchez D, Tsien A, Fleming J, Saxon A. Combined diesel exhaust particulate and ragweed allergen challenge markedly enhances human in vivo nasal ragweed-specific IgE and skews cytokine production to a T helper cell 2-type pattern. J Immunol 1997;158:2406–2413.

    CAS  PubMed  Google Scholar 

  170. Diaz-Sanchez D, Garcia MP, Wang M, Jyrala M, Saxon A. Nasal challenge with diesel exhaust particles can induce sensitization to a neoallergen in the human mucosa. J Allergy Clin Immunol 1999; 104:1183–1188.

    CAS  PubMed  Google Scholar 

  171. Takano H, Yoshikawa T, Ichinose T, Miyabara Y, Imaoka K, Sagai M. Diesel exhaust particles enhance antigen-induced airway inflammation and local cytokine expression in mice. Am J Resp Crit Care Med 1997;156:36–42.

    CAS  PubMed  Google Scholar 

  172. Takano H, Ichinose T, Miyabara Y, Yoshikawa T, Sagai M. Diesel exhaust particles enhance airway responsiveness following allergen exposure in mice. Immunopharmacol Immunotoxicol 1998;20:329–336.

    CAS  PubMed  Google Scholar 

  173. Ichinose T, Takano H, Sadakane K et al. Mouse strain differences in eosinophilic airway inflammation caused by intratracheal instillation of mite allergen and diesel exhaust particles. J Appl Toxicol 2004;24:69–76.

    CAS  PubMed  Google Scholar 

  174. Sadakane K, Ichinose T, Takano H et al. Murine strain differences in airway inflammation induced by diesel exhaust particles and house dust mite allergen. Int Arch Allergy Immunol 2002; 128:220–228.

    CAS  PubMed  Google Scholar 

  175. Finkelman FD, Yang M, Orekhova T et al. Diesel exhaust particles suppress in vivo IFN-gamma production by inhibiting cytokine effects on NK and NKT cells. J Immunol 2004; 172:3808–3813.

    CAS  PubMed  Google Scholar 

  176. Wang M, Saxon A, Diaz-Sanchez D. Early IL-production driving Th2 differentiation in a human in vivo allergic model is mast cell derived. Clin Immunol 1999;90:47–54.

    CAS  PubMed  Google Scholar 

  177. Krishna MT, Chauhan AJ, Frew AJ, Holgate ST. Toxicological mechanisms underlying oxidant pollutant-induced airway injury. Rev Environ Health 1998;13:59–71.

    CAS  PubMed  Google Scholar 

  178. May MJ, Ghosh S. Rel/NF-kappaB and I kappaB proteins: an overview. Semin Cancer Biol 1997;8:63–73.

    CAS  PubMed  Google Scholar 

  179. Ortiz LA, Lasky J, Gozal E et al. Tumor necrosis factor receptor deficiency alters matrix metalloproteinase 13/tissue inhibitor of metalloproteinase 1 expression in murine silicosis. Am J Respir Crit Care Med 2001; 163:244–252.

    CAS  PubMed  Google Scholar 

  180. Laskin DL, Sunil V, Guo Y, Heck DE, Laskin JD. Increased nitric oxide synthase in the lung after ozone inhalation is associated with activation of NF-kappaB. Environ Health Perspect 1998;106 Suppl 5:1175–1178.

    CAS  PubMed  Google Scholar 

  181. Hisada T, Adcock IM, Nasuhara Y et al. Inhibition of ozone-induced lung neutrophilia and nuclear factor-kappaB binding activity by vitamin A in rat. Eur J Pharmacol 1999;377:63–68.

    CAS  PubMed  Google Scholar 

  182. Takizawa H, Ohtoshi T, Kawasaki S et al. Diesel exhaust particles induce NF-kappaB activation in human bronchial epithelial cells in vitro: importance in cytokine transcription. J Immunol 1999; 162:4705–4711.

    CAS  PubMed  Google Scholar 

  183. Jaspers I, Flescher E, Chen LC. Ozone-induced IL-8 expression and transcription factor binding in respiratory epithelial cells. Am J Physiol Lung Cell MolPhysiol 1997;272:L504–L511.

    CAS  Google Scholar 

  184. Nichols BG, Woods JS, Luchtel DL, Corral J, Koenig JQ. Effects of ozone exposure on nuclear factor-kappaB activation and tumor necrosis factor-alpha expression in human nasal epithelial cells. Toxicol Sci 2001;60:356–362.

    CAS  PubMed  Google Scholar 

  185. Yun YP, Joo JD, Lee JY et al. Induction of nuclear factor-kappaB activation through TAK1 and NIK by diesel exhaust particles in L2 cell lines. Toxicol Lett 2005;155:337–342.

    CAS  PubMed  Google Scholar 

  186. Ma C, Wang J, Luo J. Activation of nuclear factor kappaB by diesel exhaust particles in mouse epidermal cells through phosphatidylinositol 3-kinase/Akt signaling pathway. Biochem Pharmacol 2004;67:1975–1983.

    CAS  PubMed  Google Scholar 

  187. Takizawa H. Diesel exhaust particles and their effect on induced cytokine expression in human bronchial epithelial cells. Curr Opin Allergy Clin Immunol 2004;4:355–359.

    CAS  PubMed  Google Scholar 

  188. Kang JL, Go YH, Hur KC, Castranova V. Silica-induced nuclear factor-kappaB activation: involvement of reactive oxygen species and protein tyrosine kinase activation. J Toxicol Environ Health A 2000;60:27–46.

    CAS  PubMed  Google Scholar 

  189. Rojanasakul Y, Ye J, Chen F et al. Dependence of NF-kappaB activation and free radical generation on silica-induced TNF-alpha production in macrophages. Mol Cell Biochem 1999;200:119–125.

    CAS  PubMed  Google Scholar 

  190. Chen F, Sun SC, Kuh DC, Gaydos LJ, Demers LM. Essential role of NF-kappaB activation in silica-induced inflammatory mediator production in macrophages. Biochem Biophys Res Commun 1995;214:985–992.

    CAS  PubMed  Google Scholar 

  191. Gambelli F, Di P, Niu X et al. Phosphorylation of tumor necrosis factor receptor 1 (p55) protects macrophages from silica-induced apoptosis. J Biol Chem 2004;279:2020–2029.

    CAS  PubMed  Google Scholar 

  192. Pourazar J, Mudway IS, Samet JM et al. Diesel exhaust activates redox-sensitive transcription factors and kinases in human airways. Am J Physiol Lung Cell Mol Physiol 2005;289:L724–L730.

    CAS  PubMed  Google Scholar 

  193. Brown DM, Beswick PH, Donaldson K. Induction of nuclear translocation of NF-kappaB in epithelial cells by respirable mineral fibres. J Pathol 1999; 189:258–264.

    CAS  PubMed  Google Scholar 

  194. Cheng N, Shi X, Ye J et al. Role of transcription factor NF-kappaB in asbestos-induced TNF alpha response from macrophages. Exp Mol Pathol 1999; 66:201–210.

    CAS  PubMed  Google Scholar 

  195. Kawasaki S, Takizawa H, Takami K et al. Benzene-extracted components are important for the major activity of diesel exhaust particles: effect on interleukin-8 gene expression in human bronchial epithelial cells. Am J Respir Cell Mol Biol 2001;24:419–426.

    CAS  PubMed  Google Scholar 

  196. Dai J, Xie C, Vincent R, Churg A. Air pollution particles produce airway wall remodeling in rat tracheal explants. Am J Respir Cell Mol Biol 2003; 29:352–358.

    CAS  PubMed  Google Scholar 

  197. Albrecht C, Borm PJ, Unfried K. Signal transduction pathways relevant for neoplastic effects of fibrous and non-fibrous particles. Mutat Res 2004;553:23–35.

    CAS  PubMed  Google Scholar 

  198. Rahman I. Oxidative stress and gene transcription in asthma and chronic obstructive pulmonary disease: antioxidant therapeutic targets. Curr Drug Targets Inflamm Allergy 2002;l:291–315.

    Google Scholar 

  199. Ding M, Dong Z, Chen F et al. Asbestos induces activator protein-1 transactivation in transgenic mice. Cancer Res 1999;59:1884–1889.

    CAS  PubMed  Google Scholar 

  200. Quinlan TR, Marsh JP, Janssen YM et al. Dose-responsive increases in pulmonary fibrosis after inhalation of asbestos. Am J Respir Crit Care Med 1994; 150:200–206.

    CAS  PubMed  Google Scholar 

  201. Quinlan TR, BeruBe KA, Marsh JP et al. Patterns of inflammation, cell proliferation, and related gene expression in lung after inhalation of chrysotile asbestos. Am J Pathol 1995; 147:728–739.

    CAS  PubMed  Google Scholar 

  202. Mossman BT. Signal transduction by oxidants: look who’s talking. Free Radic Biol Med 2000;28:1315–1316.

    CAS  PubMed  Google Scholar 

  203. Flaherty DM, Monick MM, Carter AB, Peterson MW, Hunninghake GW. Oxidant-mediated increases in redox factor-1 nuclear protein and activator protein-1 DNA binding in asbestos-treated macrophages. J Immunol 2002; 168:5675–5681.

    CAS  PubMed  Google Scholar 

  204. Li N, Venkatesan MI, Miguel A et al. Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element. J. Immunol 2000; 165:3393–3401.

    CAS  PubMed  Google Scholar 

  205. Ganster RW, Taylor BS, Shao L, Geller DA. Complex regulation of human inducible nitric oxide synthase gene transcription by Stat 1 and NF-kappaB. Proc Natl Acad Sci U S A 2001;98:8638–8643.

    CAS  PubMed  Google Scholar 

  206. Laskin DL, Fakhrzadeh L, Heck DE, Gerecke D, Laskin JD. Upregulation of phosphoinositide 3-kinase and protein kinase B in alveolar macrophages following ozone inhalation. Role of NF-kappaB and STAT-1 in ozone-induced nitric oxide production and toxicity. Mol Cell Biochem 2002;234-235:91–98.

    PubMed  Google Scholar 

  207. Kang JL, Lee HS, Pack IS, Hur KC, Castranova V. Phosphoinositide 3-kinase activity leads to silica-induced NF-kappaB activation through interacting with tyrosine-phosphorylated IkappaB-alpha and contributing to tyrosine phosphorylation of p65 NF-kappaB. Mol Cell Biochem 2003;248:17–24.

    CAS  PubMed  Google Scholar 

  208. Cummins AB, Palmer C, Mossman BT, Taatjes DJ. Persistent localization of activated extracellular signal-regulated kinases (ERK1/2) is epithelial cellspecific in an inhalation model of asbestosis. Am J Pathol 2003;162:713–720.

    CAS  PubMed  Google Scholar 

  209. Fubini B, Hubbard A. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radic Biol Med 2003;34:1507–1516.

    CAS  PubMed  Google Scholar 

  210. Robledo R, Mossman B. Cellular and molecular mechanisms of asbestos-induced fibrosis. J Cell Physiol 1999;180:158–166.

    CAS  PubMed  Google Scholar 

  211. Yuan Z, Taatjes DJ, Mossman BT, Heintz NH. The duration of nuclear extracellular signal-regulated kinase 1 and 2 signaling during cell cycle reentry distinguishes proliferation from apoptosis in response to asbestos. Cancer Res 2004;64:6530–6536.

    CAS  PubMed  Google Scholar 

  212. Geist LJ, Powers LS, Monick MM, Hunninghake GW. Asbestos stimulation triggers differential cytokine release from human monocytes and alveolar macrophages. Exp Lung Res 2000;26:41–56.

    CAS  PubMed  Google Scholar 

  213. Robledo RF, Buder-Hoffmann SA, Cummins AB, Walsh ES, Taatjes DJ, Mossman BT. Increased phosphorylated extracellular signal-regulated kinase immunoreactivity associated with proliferative and morphologic lung alterations after chrysotile asbestos inhalation in mice. Am J Pathol 2000;156:1307–1316.

    CAS  PubMed  Google Scholar 

  214. Zhang Q, Kleeberger SR, Reddy SP. DEP-induced fra-1 expression correlates with a distinct activation of AP-1-dependent gene transcription in the lung. Am J Physiol Lung Cell Mol Physiol 2004;286:L427–L436.

    CAS  PubMed  Google Scholar 

  215. Hashimoto S, Matsumoto K, Gon Y et al. p38 MAP kinase regulates TNF alpha-, IL-1 alpha-and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells. Clin Exp Allergy 2000;30:48–55.

    CAS  PubMed  Google Scholar 

  216. Bonvallot V, Baeza-Squiban A, Baulig A et al. Organic compounds from diesel exhaust particles elicit a proinflammatory response in human airway epithelial cells and induce cytochrome p450 1A1 expression. Am J Respir Cell Mol Biol 2001;25:515–521.

    CAS  PubMed  Google Scholar 

  217. Ohtoshi T, Takizawa H, Okazaki H et al. Diesel exhaust particles stimulate human airway epithelial cells to produce cytokines relevant to airway inflammation in vitro. J Allergy Clin Immunol 1998;101:778–785.

    CAS  PubMed  Google Scholar 

  218. Ovrevik J, Lag M, Schwarze P, efsnes M. p38 and Src-ERK1/2 pathways regulate crystalline silica-induced chemokine release in pulmonary epithelial cells. Toxicol Sci 2004;81:480–490.

    CAS  PubMed  Google Scholar 

  219. Dai J, Churg A. Relationship of fiber surface iron and active oxygen species to expression of procollagen, PDGF-A, and TGF-betal in trach’eal explants exposed to amosite asbestos. Am J Respir Cell Mol Biol 2001;24:427–435.

    CAS  PubMed  Google Scholar 

  220. Atis S, Tutluoglu B, Levant E et al. The respiratory effects of occupational polypropylene flock exposure. Eur Respir J. 2005;25:110–117.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ

    Debra L. Laskin, Vasanthi R. Sunil, Robert J. Laumbach & Howard M. Kipen

  2. Environmental and Occupational Health Sciences Institute, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ

    Debra L. Laskin, Robert J. Laumbach & Howard M. Kipen

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  1. Debra L. Laskin
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  2. Vasanthi R. Sunil
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  1. DyPort Vaccine Company, LLC, Frederick, MD

    Robert V. House

  2. Poison Center and Pharmacovigilance Unit, Lyon Cedex, France

    Jacques Descotes

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Laskin, D.L., Sunil, V.R., Laumbach, R.J., Kipen, H.M. (2007). Inflammatory Cytokines and Lung Toxicity. In: House, R.V., Descotes, J. (eds) Cytokines in Human Health. Methods in Pharmacology and Toxicology. Humana Press. https://doi.org/10.1007/978-1-59745-350-9_6

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