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Review article: Biomedical intelligence

Vol. 142 No. 1718 (2012)

Air pollution and epigenetics: effects on SP-A and innate host defence in the lung

  • Patricia Silveyra
  • Joanna Floros
DOI
https://doi.org/10.4414/smw.2012.13579
Cite this as:
Swiss Med Wkly. 2012;142:w13579
Published
22.04.2012

Abstract

An appropriate immune and inflammatory response is key to defend against harmful agents present in the environment, such as pathogens, allergens and inhaled pollutants, including ozone and particulate matter. Air pollution is a serious public health concern worldwide, and cumulative evidence has revealed that air pollutants contribute to epigenetic variation in several genes, and this in turn can contribute to disease susceptibility. Several groups of experts have recently reviewed findings on epigenetics and air pollution [1–6]. Surfactant proteins play a central role in pulmonary host defence by mediating pathogen clearance, modulating allergic responses and facilitating the resolution of lung inflammation. Recent evidence indicates that surfactant proteins are subject to epigenetic regulation under hypoxia and other conditions. Oxidative stress caused by ozone, and exposure to particulate matter have been shown to affect the expression of surfactant protein A (SP-A), an important lung host defence molecule, as well as alter its functions. In this review, we discuss recent findings in the fields of epigenetics and air pollution effects on innate immunity, with the focus on SP-A, and the human SP-A variants in particular. Their function may be differentially affected by pollutants and specifically by ozone-induced oxidative stress, and this in turn may differentially affect susceptibility to lung disease.

References

  1. Herceg Z, Vaissière T. Epigenetic mechanisms and cancer: an interface between the environment and the genome. Epigenetics. 2011;6(7):804–19.
  2. Hou L, Wang D, Baccarelli A. Environmental chemicals and microRNAs. Mutat Res. 2011;714(1–2):105–12.
  3. Bollati V, Baccarelli A. Environmental epigenetics. Heredity. 2010;105(1):105–12.
  4. Weidman JR, Dolinoy DC, Murphy SK, Jirtle RL. Cancer susceptibility: epigenetic manifestation of environmental exposures. Cancer J. 2007;13(1):9–16.
  5. Faulk C, Dolinoy DC. Timing is everything: the when and how of environmentally induced changes in the epigenome of animals. Epigenetics. 2011;6(7):791–7.
  6. Choudhuri S, Cui Y, Klaassen CD. Molecular targets of epigenetic regulation and effectors of environmental influences. Toxicol Appl Pharmacol. 2010;245(3):378–93.
  7. Brunekreef B. The continuing challenge of air pollution. Eur Respir J. 2010;36(4):704–5.
  8. Chen B, Kan H. Air pollution and population health: a global challenge. Environ Health Prev Med. 2008;13(2):94–101.
  9. Lewtas J. Air pollution combustion emissions: characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects. Mutat Res. 2007;636(1–3):95–133.
  10. Ciencewicki J, Trivedi S, Kleeberger SR. Oxidants and the pathogenesis of lung diseases. J Allergy Clin Immunol. 2008;122(3):456–68; quiz 469–70.
  11. Romieu I, Moreno-Macias H, London SJ. Gene by environment interaction and ambient air pollution. Proc Am Thorac Soc. 2010;7(2):116–22.
  12. Hassing C, Twickler M, Brunekreef B, Cassee F, Doevendans P, Kastelein J, et al. Particulate air pollution, coronary heart disease and individual risk assessment: a general overview. Eur J Cardiovasc Prev Rehabil. 2009;16(1):10–5.
  13. Perez L, Rapp R, Künzli N. The Year of the Lung: outdoor air pollution and lung health. Swiss Med Wkly. 2010;140:w13129.
  14. Jardim MJ. microRNAs: Implications for air pollution research. Mutat Res. 2011.
  15. Bayarsaihan D. Epigenetic mechanisms in inflammation. J Dent Res. 2011;90(1):9–17.
  16. Luco RF, Allo M, Schor IE, Kornblihtt AR, Misteli T. Epigenetics in alternative pre-mRNA splicing. Cell. 2011;144(1):16–26.
  17. Kampa M, Castanas E. Human health effects of air pollution. Environ Pollut. 2008;151(2):362–7.
  18. Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, et al. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med. 2009;179(7):572–8.
  19. Floros J, Thomas N. Genetic variations of surfactant proteins and lung injury. Nakos G, Papathanasiou A (eds). In: Surfactant pathogenesis and treatment of lung disease. edn. Edited by Research Signpost K, India; 2009. p. 25–48.
  20. Floros J, Pavlovic J. Genetics of acute respiratory distress syndrome: challenges, approaches, surfactant proteins as candidate genes. Semin Respir Crit Care Med. 2003;24(2):161–8.
  21. Floros J, Phelps DS. Pulmonary surfactant. In: Yaksh TL, et al. (eds). Anesthesia: biologic foundations. Philadelphia: Lippincott-Raven Publishers; 1997. p. 1259–80.
  22. Vaid M, Floros J. Surfactant protein DNA methylation: a new entrant in the field of lung cancer diagnostics? (Review). Oncol Rep. 2009;21(1):3–11.
  23. Silveyra P, Floros J. Genetic variant associations of human SP-A and SP-D with acute and chronic lung injury. Front Biosci. 2012;17:407–29.
  24. Lin Z, Thomas NJ, Bibikova M, Seifart C, Wang Y, Guo X, et al. DNA methylation markers of surfactant proteins in lung cancer. Int J Oncol. 2007;31(1):181–91.
  25. Wang G, Guo X, Silveyra P, Kimball S, Floros J. Cap-independent translation of human SP-A 5'-UTR variants: a double-loop structure and cis-element contribution. Am J Physiol Lung Cell Mol Physiol. 2009;296(4):L635–47.
  26. Mikerov A, Umstead T, Gan X, Huang W, Guo X, Wang G, et al. Impact of ozone exposure on the phagocytic activity of human surfactant protein A (SP-A) and SP-A variants. Am J Physiol Lung Cell Mol Physiol. 2008;294(1):L121–30.
  27. Durrani F, Phelps DS, Weisz J, Silveyra P, Hu S, Mikerov AN, et al. Gonadal hormones and oxidative stress interaction differentially affects survival of male and female mice after lung Klebsiella Pneumoniae infection. Exp Lung Res. 2011;38(4):165–72.
  28. Samet JM. The Clean Air Act and health – a clearer view from 2011. N Engl J Med. 2011;365(3):198–201.
  29. Bernstein JA, Alexis N, Bacchus H, Bernstein IL, Fritz P, Horner E, et al. The health effects of non-industrial indoor air pollution. J Allergy Clin Immunol. 2008;121(3):585–91.
  30. Ostro B, Lipsett M, Reynolds P, Goldberg D, Hertz A, Garcia C, et al. Long-term exposure to constituents of fine particulate air pollution and mortality: results from the California Teachers Study. Environ Health Perspect. 2010;118(3):363–9.
  31. Guxens M, Sunyer J. A review of epidemiological studies on neuropsychological effects of air pollution. Swiss Med Wkly. 2012;141:w13322.
  32. Bernstein JA, Alexis N, Barnes C, Bernstein IL, Nel A, Peden D, et al. Health effects of air pollution. J Allergy Clin Immunol. 2004;114(5):1116–23.
  33. McCreanor J, Cullinan P, Nieuwenhuijsen MJ, Stewart-Evans J, Malliarou E, Jarup L, et al. Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med. 2007;357(23):2348–58.
  34. Riedl MA. The effect of air pollution on asthma and allergy. Curr Allergy Asthma Rep. 2008;8(2):139–46.
  35. Hollingsworth JW, Kleeberger SR, Foster WM. Ozone and pulmonary innate immunity. Proc Am Thorac Soc. 2007;4(3):240–6.
  36. Smith KR, Jerrett M, Anderson HR, Burnett RT, Stone V, Derwent R, et al. Public health benefits of strategies to reduce greenhouse-gas emissions: health implications of short-lived greenhouse pollutants. Lancet. 2009;374(9707):2091–103.
  37. Jerrett M, Burnett RT, Pope CA, 3rd, Ito K, Thurston G, Krewski D, et al. Long-term ozone exposure and mortality. N Engl J Med. 2009;360(11):1085–95.
  38. Kim CS, Alexis NE, Rappold AG, Kehrl H, Hazucha MJ, Lay JC, et al. Lung function and inflammatory responses in healthy young adults exposed to 0.06 ppm ozone for 6.6 hours. Am J Respir Crit Care Med. 2011;183(9):1215–21.
  39. Becker S, Madden MC, Newman SL, Devlin RB, Koren HS. Modulation of human alveolar macrophage properties by ozone exposure in vitro. Toxicol Appl Pharmacol. 1991;110(3):403–15.
  40. Selgrade MK, Illing JW, Starnes DM, Stead AG, Menache MG, Stevens MA. Evaluation of effects of ozone exposure on influenza infection in mice using several indicators of susceptibility. Fundam Appl Toxicol. 1988;11(1):169–80.
  41. Mikerov AN, Gan X, Umstead TM, Miller L, Chinchilli VM, Phelps DS, et al. Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection. Respir Res. 2008;9:24.
  42. Mikerov AN, Haque R, Gan X, Guo X, Phelps DS, Floros J. Ablation of SP-A has a negative impact on the susceptibility of mice to Klebsiella pneumoniae infection after ozone exposure: sex differences. Respir Res. 2008;9:77.
  43. Haque R, Umstead TM, Ponnuru P, Guo X, Hawgood S, Phelps DS, et al. Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice. Toxicol Appl Pharmacol. 2007;220(1):72–82.
  44. Janic B, Umstead TM, Phelps DS, Floros J. Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation. Am J Physiol Lung Cell Mol Physiol. 2005;288(2):L317–25.
  45. Gilmour MI, Hmieleski RR, Stafford EA, Jakab GJ. Suppression and recovery of the alveolar macrophage phagocytic system during continuous exposure to 0.5 ppm ozone. Exp Lung Res. 1991;17(3):547–58.
  46. Wang G, Umstead TM, Phelps DS, Al-Mondhiry H, Floros J. The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production. Environ Health Perspect. 2002;110(1):79–84.
  47. Huang W, Wang G, Phelps DS, Al-Mondhiry H, Floros J. Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: effect of ozone-induced SP-A oxidation. Am J Physiol Lung Cell Mol Physiol. 2004;286(3):L546–53.
  48. Durham AL, Wiegman C, Adcock IM. Epigenetics of asthma. Biochim Biophys Acta. 2011.
  49. Madrigano J, Baccarelli A, Mittleman MA, Wright RO, Sparrow D, Vokonas PS, et al. Prolonged exposure to particulate pollution, genes associated with glutathione pathways, and DNA methylation in a cohort of older men. Environ Health Perspect. 2011;119(7):977–82.
  50. Probst AV, Dunleavy E, Almouzni G. Epigenetic inheritance during the cell cycle. Nat Rev Mol Cell Biol. 2009;10(3):192–206.
  51. Martienssen RA, Kloc A, Slotkin RK, Tanurdzić M. Epigenetic inheritance and reprogramming in plants and fission yeast. Cold Spring Harb Symp Quant Biol. 2008;73:265–71.
  52. Nafee TM, Farrell WE, Carroll WD, Fryer AA, Ismail KM. Epigenetic control of fetal gene expression. BJOG. 2008;115(2):158–68.
  53. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31(2):89–97.
  54. Shames DS, Minna JD, Gazdar AF. DNA methylation in health, disease, and cancer. Curr Mol Med. 2007;7(1):85–102.
  55. Singh SM, Murphy B, O’Reilly RL. Involvement of gene-diet/drug interaction in DNA methylation and its contribution to complex diseases: from cancer to schizophrenia. Clin Genet. 2003;64(6):451–60.
  56. Wen H, Schaller MA, Dou Y, Hogaboam CM, Kunkel SL. Dendritic cells at the interface of innate and acquired immunity: the role for epigenetic changes. J Leukoc Biol. 2008;83(3):439–46.
  57. Pfefferle PI, Pinkenburg O, Renz H. Fetal epigenetic mechanisms and innate immunity in asthma. Curr Allergy Asthma Rep. 2010;10(6):434–43.
  58. Awasthi S, Madhusoodhanan R, Wolf R. Surfactant protein-A and toll-like receptor-4 modulate immune functions of preterm baboon lung dendritic cell precursor cells. Cell Immunol. 2011;268(2):87–96.
  59. Mikerov A, Umstead T, Huang W, Liu W, Phelps D, Floros J. SP-A1 and SP-A2 variants differentially enhance association of Pseudomonas aeruginosa with rat alveolar macrophages. Am J Physiol Lung Cell Mol Physiol. 2005;288(1):L150–8.
  60. Crouch EC. Collectins and pulmonary host defense. Am J Respir Cell Mol Biol. 1998;19(2):177–201.
  61. Crouch E, Hartshorn K, Ofek I. Collectins and pulmonary innate immunity. Immunol Rev. 2000;173:52–5.
  62. Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005;5(1):58–68.
  63. Mariencheck WI, Savov J, Dong Q, Tino MJ, Wright JR. Surfactant protein A enhances alveolar macrophage phagocytosis of a live, mucoid strain of P. aeruginosa. Am J Physiol. 1999;277(4 Pt 1):L777–86.
  64. Wang J, Reid K. The immunoregulatory roles of lung surfactant collectins SP-A, and SP-D, in allergen-induced airway inflammation. Immunobiology. 2007;212(4-5):417–25.
  65. Wang G, Phelps D, Umstead T, Floros J. Human SP-A protein variants derived from one or both genes stimulate TNF-alpha production in the THP-1 cell line. Am J Physiol Lung Cell Mol Physiol. 2000;278(5):L946–54.
  66. Griese M, Birrer P, Demirsoy A. Pulmonary surfactant in cystic fibrosis. Eur Respir J. 1997;10(9):1983–8.
  67. Hull J, South M, Phelan P, Grimwood K. Surfactant composition in infants and young children with cystic fibrosis. Am J Respir Crit Care Med. 1997;156(1):161–5.
  68. Postle AD, Mander A, Reid KB, Wang JY, Wright SM, Moustaki M, et al. Deficient hydrophilic lung surfactant proteins A and D with normal surfactant phospholipid molecular species in cystic fibrosis. Am J Respir Cell Mol Biol. 1999;20(1):90–8.
  69. Woodworth BA, Wood R, Baatz JE, Schlosser RJ. Sinonasal surfactant protein A1, A2, and D gene expression in cystic fibrosis: a preliminary report. Otolaryngol Head Neck Surg. 2007;137(1):34–8.
  70. Tagaram H, Wang G, Umstead T, Mikerov A, Thomas N, Graff G, et al. Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health. Am J Physiol Lung Cell Mol Physiol. 2007;292(5):L1052–63.
  71. Mikerov A, Wang G, Umstead T, Zacharatos M, Thomas N, Phelps D, et al. Surfactant protein A2 (SP-A2) variants expressed in CHO cells stimulate phagocytosis of Pseudomonas aeruginosa more than do SP-A1 variants. Infect Immun. 2007;75(3):1403–12.
  72. LeVine AM, Kurak KE, Wright JR, Watford WT, Bruno MD, Ross GF, et al. Surfactant protein-A binds group B streptococcus enhancing phagocytosis and clearance from lungs of surfactant protein-A-deficient mice. Am J Respir Cell Mol Biol. 1999;20(2):279–86.
  73. Lin Z, Wang Y, Zhu K, Floros J. Differential allele expression of host defense genes, pulmonary surfactant protein-A and osteopontin, in rat. Mol Immunol. 2004;41(12):1155–65.
  74. Benlhabib H, Mendelson CR. Epigenetic regulation of surfactant protein A gene (SP-A) expression in fetal lung reveals a critical role for Suv39h methyltransferases during development and hypoxia. Mol Cell Biol. 2011;31(10):1949–58.
  75. Islam KN, Mendelson CR. Permissive effects of oxygen on cyclic AMP and interleukin-1 stimulation of surfactant protein A gene expression are mediated by epigenetic mechanisms. Mol Cell Biol. 2006;26(8):2901–12.
  76. Islam KN, Mendelson CR. Glucocorticoid/glucocorticoid receptor inhibition of surfactant protein-A (SP-A) gene expression in lung type II cells is mediated by repressive changes in histone modification at the SP-A promoter. Mol Endocrinol. 2008;22(3):585–96.
  77. Silveyra P, Wang G, Floros J. Human SP-A1 (SFTPA1) variant-specific 3' UTRs and poly(A) tail differentially affect the in vitro translation of a reporter gene. Am J Physiol Lung Cell Mol Physiol. 2010;299(4):L523–34.
  78. Wang G, Guo X, Floros J. Differences in the translation efficiency and mRNA stability mediated by 5'-UTR splice variants of human SP-A1 and SP-A2 genes. Am J Physiol Lung Cell Mol Physiol. 2005;289(3):L497–508.
  79. Silveyra P, Raval M, Simmons BP, Diangelo S, Wang G, Floros J. The untranslated exon B of human surfactant protein A2 (SFTPA2) mRNAs is an enhancer for transcription and translation. Am J Physiol Lung Cell Mol Physiol. 2011.
  80. Sandoval J, Heyn HA, Moran S, Serra-Musach J, Pujana MA, Bibikova M, et al. Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics. 2011;6(6):692–702.
  81. Müller B, Seifart C, Barth PJ. Effect of air pollutants on the pulmonary surfactant system. Eur J Clin Invest. 1998;28(9):762–77.
  82. Mikerov AN, Cooper TK, Wang G, Hu S, Umstead TM, Phelps DS, et al. Histopathologic evaluation of lung and extrapulmonary tissues show sex differences in Klebsiella pneumoniae – infected mice under different exposure conditions. Int J Physiol Pathophysiol Pharmacol. 2011;3(3):176–90.
  83. Bruce SR, Atkins CL, Colasurdo GN, Alcorn JL. Respiratory syncytial virus infection alters surfactant protein A expression in human pulmonary epithelial cells by reducing translation efficiency. Am J Physiol Lung Cell Mol Physiol. 2009;297(4):L559–67.
  84. Wang Y, Voelker DR, Lugogo NL, Wang G, Floros J, Ingram JL, et al. Surfactant protein-A is defective in abrogating inflammation in asthma. Am J Physiol Lung Cell Mol Physiol. 2011.
  85. Wang G, Bates-Kenney S, Tao J, Phelps D, Floros J. Differences in biochemical properties and in biological function between human SP-A1 and SP-A2 variants, and the impact of ozone-induced oxidation. Biochemistry. 2004;43(14):4227–39.