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BioMed Research International
Volume 2013 (2013), Article ID 420497, 8 pages
http://dx.doi.org/10.1155/2013/420497
Review Article

Self-Eating: Friend or Foe? The Emerging Role of Autophagy in Idiopathic Pulmonary Fibrosis

1Interstitial Lung Disease Unit, University Hospital of Heraklion, 71110 Heraklion, Crete, Greece
2Laboratory of Virology, Medical School, University of Crete, 71110 Heraklion, Crete, Greece

Received 27 December 2012; Revised 27 February 2013; Accepted 27 February 2013

Academic Editor: Sharbel Weidner Maluf

Copyright © 2013 George A. Margaritopoulos et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. A. Margaritopoulos, M. Romagnoli, V. Poletti, N. M. Siafakas, A. U. Wells, and K. M. Antoniou, “Recent advances in the pathogenesis and clinical evaluation of pulmonary fibrosis,” European Respiratory Review, vol. 21, no. 123, pp. 48–56, 2012. View at Google Scholar
  2. C. Vancheri, “Idiopathic pulmonary fibrosis: an altered fibroblast proliferation linked to cancer biology,” Proceedings of the American Thoracic Society, vol. 9, pp. 153–157, 2012. View at Google Scholar
  3. H. Taniguchi, M. Ebina, Y. Kondoh et al., “Pirfenidone in idiopathic pulmonary fibrosis,” European Respiratory Journal, vol. 35, pp. 821–829, 2010. View at Google Scholar
  4. M. Demedts, J. Behr, R. Buhl et al., “High-dose acetylcysteine in idiopathic pulmonary fibrosis,” The New England Journal of Medicine, vol. 353, no. 21, pp. 2229–2242, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. A. S. Patel, L. Lin, A. Geyer et al., “Autophagy in idiopathic pulmonary fibrosis,” PLoS One, vol. 7, Article ID e41394, 2012. View at Google Scholar
  6. J. Araya, J. Kojima, N. Takasaka et al., “Insufficient autophagy in idiopathic pulmonary fibrosis,” American Journal of Physiology, vol. 4, no. 1, pp. 56–69, 2013. View at Google Scholar
  7. J. A. Haspel and A. M. Choi, “Autophagy:a core cellular process with emerging links to pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 184, pp. 1237–1246, 2011. View at Google Scholar
  8. I. Kim, S. Rodriguez-Enriquez, and J. J. Lemasters, “Selective degradation of mitochondria by mitophagy,” Archives of Biochemistry and Biophysics, vol. 462, no. 2, pp. 245–253, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. B. Levine, “Eating oneself and uninvited guests: autophagy-related pathways in cellular defense,” Cell, vol. 120, no. 2, pp. 159–162, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. B. Levine, S. Sinha, and G. Kroemer, “Bcl-2 family members: dual regulators of apoptosis and autophagy,” Autophagy, vol. 4, no. 5, pp. 600–606, 2008. View at Google Scholar · View at Scopus
  11. N. Mizushima and M. Komatsu, “Autophagy: renovation of cells and tissues,” Cell, vol. 147, pp. 728–741, 2011. View at Google Scholar
  12. E. Itakura, C. Kishi, K. Inoue, and N. Mizushima, “Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG,” Molecular Biology of the Cell, vol. 19, no. 12, pp. 5360–5372, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. M. G. Gutierrez, D. B. Munafó, W. Berón, and M. I. Colombo, “Rab7 is required for the normal progression of the autophagic pathway in mammalian cells,” Journal of Cell Science, vol. 117, no. 13, pp. 2687–2697, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Jäger, C. Bucci, I. Tanida et al., “Role for Rab7 in maturation of late autophagic vacuoles,” Journal of Cell Science, vol. 117, no. 20, pp. 4837–4848, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. Y. Ohsumi and N. Mizushima, “Two ubiquitin-like conjugation systems essential for autophagy,” Seminars in Cell and Developmental Biology, vol. 15, no. 2, pp. 231–236, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. H. He, Y. Dang, F. Dai et al., “Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B,” The Journal of Biological Chemistry, vol. 278, no. 31, pp. 29278–29287, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. Y. Kabeya, N. Mizushima, T. Ueno et al., “LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing,” EMBO Journal, vol. 19, no. 21, pp. 5720–5728, 2000. View at Google Scholar · View at Scopus
  18. J. M. Swanlund, K. C. Kregel, and T. D. Oberley, “Investigating autophagy: quantitative morphometric analysis using electron microscopy,” Autophagy, vol. 6, no. 2, pp. 270–277, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. D. J. Klionsky, H. Abeliovich, P. Agostinis et al., “Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes,” Autophagy, vol. 4, no. 2, pp. 151–175, 2008. View at Google Scholar · View at Scopus
  20. N. Mizushima and T. Yoshimori, “How to interpret LC3 immunoblotting,” Autophagy, vol. 3, no. 6, pp. 542–545, 2007. View at Google Scholar · View at Scopus
  21. S. Pankiv, T. H. Clausen, T. Lamark et al., “P62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy,” The Journal of Biological Chemistry, vol. 282, no. 33, pp. 24131–24145, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. G. Bjørkøy, T. Lamark, S. Pankiv, A. Øvervatn, A. Brech, and T. Johansen, “Monitoring autophagic degradation of p62/sqstm1,” Methods in Enzymology, vol. 451, pp. 181–197, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. N. Mizushima, T. Yoshimori, and B. Levine, “Methods in mammalian autophagy research,” Cell, vol. 140, no. 3, pp. 313–326, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. Z. H. Chen, H. P. Kim, F. C. Sciurba et al., “Egr-1 regulates autophagy in cigarette smoke-induced chronic obstructive pulmonary disease,” PLoS One, vol. 3, no. 10, Article ID e3316, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. M. M. Monick, L. S. Powers, K. Walters et al., “Identification of an autophagy defect in smokers' alveolar macrophages,” Journal of Immunology, vol. 185, no. 9, pp. 5425–5435, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. http://www.clinicaltrials.gov/.
  27. P. K. Hong, X. Wang, Z. H. Chen et al., “Autophagic proteins regulate cigarette smoke-induced apoptosis: protective role of heme oxygenase-1,” Autophagy, vol. 4, no. 7, pp. 887–895, 2008. View at Google Scholar · View at Scopus
  28. J. W. Hwang, S. Chung, I. K. Sundar et al., “Cigarette smoke-induced autophagy is regulated by SIRT1-PARP-1-dependent mechanism: implication in pathogenesis of COPD,” Archives of Biochemistry and Biophysics, vol. 500, no. 2, pp. 203–209, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. Z. H. Chen, H. C. Lam, Y. Jin et al., “Autophagy protein microtubule associated protein 1 light chain-3b (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, pp. 18880–18885, 2010. View at Google Scholar
  30. A. Luciani, V. R. Villella, S. Esposito et al., “Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition,” Nature Cell Biology, vol. 12, no. 9, pp. 863–875, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. B. A. Abdulrahman, A. A. Khweek, A. Akhter et al., “Autophagy stimulation by rapamycin suppresses lung inflammation and infection by burkholderia cenocepacia in a model of cystic fibrosis,” Autophagy, vol. 7, pp. 1359–1370, 2011. View at Google Scholar
  32. V. Deretic, S. Singh, S. Master et al., “Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism,” Cellular Microbiology, vol. 8, no. 5, pp. 719–727, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. S. B. Singh, A. S. Davis, G. A. Taylor, and V. Deretic, “Human IRGM induces autophagy to eliminate intracellular mycobacteria,” Science, vol. 313, no. 5792, pp. 1438–1441, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. M. G. Gutierrez, S. S. Master, S. B. Singh, G. A. Taylor, M. I. Colombo, and V. Deretic, “Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages,” Cell, vol. 119, no. 6, pp. 753–766, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. S. J. Lee, A. Smith, L. Guo et al., “Autophagic protein LC3B confers resistance against hypoxia-induced pulmonary hypertension,” American Journal of Respiratory and Critical Care Medicine, vol. 183, no. 5, pp. 649–658, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Parkhitko, F. Myachina, T. A. Morrison et al., “Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 30, pp. 12455–12460, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. J. H. Zhang, C. D. Fan, B. X. Zhao et al., “Synthesis and preliminary biological evaluation of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as potential agents against A549 lung cancer cells,” Bioorganic and Medicinal Chemistry, vol. 16, no. 24, pp. 10165–10171, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. Q. He, B. Huang, J. Zhao, Y. Zhang, S. Zhang, and J. Miao, “Knockdown of integrin β4-induced autophagic cell death associated with P53 in A549 lung adenocarcinoma cells,” FEBS Journal, vol. 275, no. 22, pp. 5725–5732, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. J. J. Gills, J. LoPiccolo, J. Tsurutani et al., “Nelfinavir, a lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and invivo,” Clinical Cancer Research, vol. 13, no. 17, pp. 5183–5194, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. H. Tanjore, D. S. Cheng, A. L. Degryse et al., “Alveolar epithelial cells undergo epithelial-to-mesenchymal transition in response to endoplasmic reticulum stress,” The Journal of Biological Chemistry, vol. 286, pp. 30972–30980, 2011. View at Google Scholar
  41. C. R. Kliment and T. D. Oury, “Oxidative stress, extracellular matrix targets, and idiopathic pulmonary fibrosis,” Free Radical Biology and Medicine, vol. 49, no. 5, pp. 707–717, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Tzouvelekis, V. Harokopos, T. Paparountas et al., “Comparative expression profiling in pulmonary fibrosis suggests a role of hypoxia-inducible factor-1α in disease pathogenesis,” American Journal of Respiratory and Critical Care Medicine, vol. 176, no. 11, pp. 1108–1119, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. T. Yorimitsu, U. Nair, Z. Yang, and D. J. Klionsky, “Endoplasmic reticulum stress triggers autophagy,” The Journal of Biological Chemistry, vol. 281, no. 40, pp. 30299–30304, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Kiffin, U. Bandyopadhyay, and A. M. Cuervo, “Oxidative stress and autophagy,” Antioxidants and Redox Signaling, vol. 8, no. 1-2, pp. 152–162, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. H. Zhang, M. Bosch-Marce, L. A. Shimoda et al., “Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia,” The Journal of Biological Chemistry, vol. 283, pp. 10892–10903, 2008. View at Google Scholar
  46. C. Xu, B. Bailly-Maitre, and J. C. Reed, “Endoplasmic reticulum stress: cell life and death decisions,” The Journal of Clinical Investigation, vol. 115, no. 10, pp. 2656–2664, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Ogata, S. Hino, A. Saito et al., “Autophagy is activated for cell survival after endoplasmic reticulum stress,” Molecular and Cellular Biology, vol. 26, pp. 9220–9231, 2006. View at Google Scholar
  48. W. X. Ding, H. M. Ni, W. Gao et al., “Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival,” The Journal of Biological Chemistry, vol. 282, pp. 4702–4710, 2007. View at Google Scholar
  49. S. H. Oh and S. C. Lim, “Endoplasmic reticulum stress-mediated autophagy/apoptosis induced by capsaicin (8-methyl-N-vanillyl-6-nonenamide) and dihydrocapsaicin is regulated by the extent of c-jun NH2-terminal kinase/extracellular signal-regulated kinase activation in WI38 lung epithelial fibroblast cells,” Journal of Pharmacology and Experimental Therapeutics, vol. 329, no. 1, pp. 112–122, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. L. M. Nogee, A. E. Dunbar III, S. E. Wert, F. Askin, A. Hamvas, and J. A. Whitsett, “A mutation in the surfactant protein C gene associated with familial interstitial lung disease,” The New England Journal of Medicine, vol. 344, no. 8, pp. 573–579, 2001. View at Publisher · View at Google Scholar · View at Scopus
  51. A. Q. Thomas, K. Lane, J. Phillips III et al., “Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred,” American Journal of Respiratory and Critical Care Medicine, vol. 165, no. 9, pp. 1322–1328, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. W. J. Wang, S. Mulugeta, S. J. Russo, and M. F. Beers, “Deletion of exon 4 from human surfactant protein C results in aggresome formation and generation of a dominant negative,” Journal of Cell Science, vol. 116, no. 4, pp. 683–692, 2003. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Mulugeta, V. Nguyen, S. J. Russo, M. Muniswamy, and M. F. Beers, “A surfactant protein C precursor protein BRICHOS domain mutation causes endoplasmic reticulum stress, proteasome dysfunction, and caspase 3 activation,” American Journal of Respiratory Cell and Molecular Biology, vol. 32, no. 6, pp. 521–530, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Korfei, C. Ruppert, P. Mahavadi et al., “Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis,” American Journal of Respiratory and Critical Care Medicine, vol. 178, pp. 838–846, 2008. View at Google Scholar
  55. U. T. Brunk, H. Dalen, K. Roberg, and H. B. Hellquist, “Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts,” Free Radical Biology and Medicine, vol. 23, no. 4, pp. 616–626, 1997. View at Publisher · View at Google Scholar · View at Scopus
  56. Y. Chen, E. McMillan-Ward, J. Kong, S. J. Israels, and S. B. Gibson, “Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells,” Cell Death and Differentiation, vol. 15, no. 1, pp. 171–182, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. R. Scherz-Shouval, E. Shvets, E. Fass, H. Shorer, L. Gil, and Z. Elazar, “Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4,” EMBO Journal, vol. 26, no. 7, pp. 1749–1760, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. I. Rahman, E. Skwarska, M. Henry et al., “Systemic and pulmonary oxidative stress in idiopathic pulmonary fibrosis,” Free Radical Biology and Medicine, vol. 27, no. 1-2, pp. 60–68, 1999. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Teramoto, Y. Fukuchi, Y. Uejima, C. Y. Shu, and H. Orimo, “Superoxide anion formation and glutathione metabolism of blood in patients with idiopathic pulmonary fibrosis,” Biochemical and Molecular Medicine, vol. 55, no. 1, pp. 66–70, 1995. View at Publisher · View at Google Scholar · View at Scopus
  60. Z. D. Daniil, E. Papageorgiou, A. Koutsokera et al., “Serum levels of oxidative stress as a marker of disease severity in idiopathic pulmonary fibrosis,” Pulmonary Pharmacology and Therapeutics, vol. 21, no. 1, pp. 26–31, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. A. M. Cantin, R. C. Hubbard, and R. G. Crystal, “Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis,” American Review of Respiratory Disease, vol. 139, no. 2, pp. 370–372, 1989. View at Google Scholar · View at Scopus
  62. J. Behr, K. Maier, B. Degenkolb, F. Krombach, and C. Vogelmeier, “Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression,” American Journal of Respiratory and Critical Care Medicine, vol. 156, no. 6, pp. 1897–1901, 1997. View at Google Scholar · View at Scopus
  63. J. Behr, B. Degenkolb, F. Krombach, and C. Vogelmeier, “Intracellular glutathione and bronchoalveolar cells in fibrosing alveolitis: effects of N-acetylcysteine,” European Respiratory Journal, vol. 19, no. 5, pp. 906–911, 2002. View at Publisher · View at Google Scholar · View at Scopus
  64. J. Behr, M. Demedts, R. Buhl et al., “Lung function in idiopathic pulmonary fibrosis–extended analyses of the IFIGENIA trial,” Respiratory Research, vol. 10, article 101, 2009. View at Google Scholar
  65. Idiopathic Pulmonary Fibrosis Clinical Research Network, G. Raghu, K. J. Anstrom, T. E. King Jr., J. A. Lasky, and F. J. Martinez, “Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis,” The New England Journal of Medicine, vol. 366, pp. 1968–1977, 2012. View at Google Scholar
  66. G. Bellot, R. Garcia-Medina, P. Gounon et al., “Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains,” Molecular and Cellular Biology, vol. 29, no. 10, pp. 2570–2581, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. M. B. Azad, Y. Chen, E. S. Henson et al., “Hypoxia induces autophagic cell death in apoptosis-competent cells through a mechanism involving BNIP3,” Autophagy, vol. 4, no. 2, pp. 195–204, 2008. View at Google Scholar · View at Scopus
  68. A. Orvedahl, D. Alexander, Z. Tallóczy et al., “HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein,” Cell Host and Microbe, vol. 1, no. 1, pp. 23–35, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. Z. Tallóczy, W. Jiang, H. W. Virgin 4th et al., “Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, pp. 190–195, 2002. View at Google Scholar
  70. B. He, M. Gross, and B. Roizman, “The γ134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 3, pp. 843–848, 1997. View at Google Scholar · View at Scopus
  71. M. Mulvey, J. Poppers, D. Sternberg, and I. Mohr, “Regulation of eIF2α phosphorylation by different functions that act during discrete phases in the herpes simplex virus type 1 life cycle,” Journal of Virology, vol. 77, no. 20, pp. 10917–10928, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. M. Chaumorcel, M. Lussignol, L. Mouna et al., “The human cytomegalovirus protein TRS1 inhibits autophagy via its interaction with Beclin 1,” Journal of Virology, vol. 86, pp. 2571–2584, 2012. View at Google Scholar
  73. A. Cuconati and E. White, “Viral homologs of BCL-2: role of apoptosis in the regulation of virus infection,” Genes and Development, vol. 16, no. 19, pp. 2465–2478, 2002. View at Publisher · View at Google Scholar · View at Scopus
  74. Y. W. Tang, J. E. Johnson, P. J. Browning et al., “Herpesvirus DNA is consistently detected in lungs of patients with idiopathic pulmonary fibrosis,” Journal of Clinical Microbiology, vol. 41, no. 6, pp. 2633–2640, 2003. View at Google Scholar · View at Scopus
  75. J. J. Egan, J. P. Stewart, P. S. Hasleton, J. R. Arrand, K. B. Carroll, and A. A. Woodcock, “Epstein-Barr virus replication within pulmonary epithelial cells in cryptogenic fibrosing alveolitis,” Thorax, vol. 50, no. 12, pp. 1234–1239, 1995. View at Google Scholar · View at Scopus
  76. J. P. Stewart, J. J. Egan, A. J. Ross et al., “The detection of Epstein-Barr virus DNA in lung tissue from patients with idiopathic pulmonary fibrosis,” American Journal of Respiratory and Critical Care Medicine, vol. 159, no. 4, pp. 1336–1341, 1999. View at Google Scholar · View at Scopus
  77. K. Tsukamoto, H. Hayakawa, A. Sato, K. Chida, H. Nakamura, and K. Miura, “Involvement of Epstein-Barr virus latent membrane protein 1 in disease progression in patients with idiopathic pulmonary fibrosis,” Thorax, vol. 55, no. 11, pp. 958–961, 2000. View at Publisher · View at Google Scholar · View at Scopus
  78. I. Lasithiotaki, K. M. Antoniou, V. M. Vlahava et al., “Detection of herpes simplex virus type-1 in patients with fibrotic lung diseases,” PLoS One, vol. 6, Article ID e27800, 2011. View at Google Scholar
  79. K. M. Vannella, T. R. Luckhardt, C. A. Wilke, L. F. van Dyk, G. B. Toews, and B. B. Moore, “Latent herpesvirus infection augments experimental pulmonary fibrosis,” American Journal of Respiratory and Critical Care Medicine, vol. 181, no. 5, pp. 465–477, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. S. Mi, Z. Li, H. Z. Yang et al., “Blocking IL-17A promotes the resolution of pulmonary inflammation and fibrosis via TGF-beta1- dependent and -independent mechanisms,” The Journal of Immunology, vol. 187, pp. 3003–3014, 2011. View at Google Scholar
  81. H. R. Collard, “The age of idiopathic pulmonary fibrosis,” American Journal of Respiratory and Critical Care Medicine, vol. 181, no. 8, pp. 771–772, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Terman, “The effect of age on formation and elimination of autophagic vacuoles in mouse hepatocytes,” Gerontology, vol. 41, supplement 2, pp. 319–326, 1995. View at Google Scholar · View at Scopus
  83. T. M. Maher, A. U. Wells, and G. J. Laurent, “Idiopathic pulmonary fibrosis: multiple causes and multiple mechanisms?” European Respiratory Journal, vol. 30, no. 5, pp. 835–839, 2007. View at Publisher · View at Google Scholar · View at Scopus