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PPAR Research
Volume 2011, Article ID 318134, 11 pages
http://dx.doi.org/10.1155/2011/318134
Research Article

Electrophilic PPARγ Ligands Attenuate IL-1β and Silica-Induced Inflammatory Mediator Production in Human Lung Fibroblasts via a PPARγ-Independent Mechanism

1Division of Pulmonary and Critical Care Medicine, University of Rochester, 601 Elmwood Avenue, P.O. Box 692, Rochester, NY 14642, USA
2Department of Environmental Medicine, University of Rochester, Rochester, NY 14642, USA
3Lung Biology and Disease Program, University of Rochester, Rochester, NY 14642, USA
4Department of Surgery, University of Rochester, Rochester, NY 14642, USA

Received 23 November 2010; Revised 4 March 2011; Accepted 25 March 2011

Academic Editor: Paul Drew

Copyright © 2011 Christopher M. Hogan 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. P. J. Barnes, “Future advances in COPD therapy,” Respiration, vol. 68, no. 5, pp. 441–448, 2001. View at Publisher · View at Google Scholar · View at Scopus
  2. D. H. Bowden and I. Y. R. Adamson, “The role of cell injury and the continuing inflammatory response in the generation of silicotic pulmonary fibrosis,” Journal of Pathology, vol. 144, no. 3, pp. 149–161, 1984. View at Google Scholar · View at Scopus
  3. J. S. Brody and A. Spira, “Chronic obstructive pulmonary disease, inflammation, and lung cancer,” Proceedings of the American Thoracic Society, vol. 3, no. 6, pp. 535–537, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. E. A. Engels, “Inflammation in the development of lung cancer: epidemiological evidence,” Expert Review of Anticancer Therapy, vol. 8, no. 4, pp. 605–615, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. I. Issemann, R. A. Prince, J. D. Tugwood, and S. Green, “The peroxisome proliferator-activated receptor:retinoid X receptor heterodimer is activated by fatty acids and fibrate hypolipidaemic drugs,” Journal of Molecular Endocrinology, vol. 11, no. 1, pp. 37–47, 1993. View at Google Scholar · View at Scopus
  6. A. Cabrero, J. C. Laguna, and M. Vázquez, “Peroxisome proliferator-activated receptors and the control of inflammation,” Curr Drug Targets Inflamm Allergy, vol. 1, no. 3, pp. 243–248, 2002. View at Google Scholar · View at Scopus
  7. N. S. Tan, L. Michalik, B. Desvergne, and W. Wahli, “Multiple expression control mechanisms of peroxisome proliferator-activated receptors and their target genes,” Journal of Steroid Biochemistry and Molecular Biology, vol. 93, no. 2–5, pp. 99–105, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. M. G. Belvisi, D. J. Hele, and M. A. Birrell, “Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation,” European Journal of Pharmacology, vol. 533, no. 1–3, pp. 101–109, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. R. Kapadia, J. H. Yi, and R. Vemuganti, “Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists,” Frontiers in Bioscience, vol. 13, no. 5, pp. 1813–1826, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Lehrke and M. A. Lazar, “The many faces of PPARγ,” Cell, vol. 123, no. 6, pp. 993–999, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. G. Rizzo and S. Fiorucci, “PPARs and other nuclear receptors in inflammation,” Current Opinion in Pharmacology, vol. 6, no. 4, pp. 421–427, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. S. A. Kliewer, J. M. Lenhard, T. M. Willson, I. Patel, D. C. Morris, and J. M. Lehmann, “A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation,” Cell, vol. 83, no. 5, pp. 813–819, 1995. View at Google Scholar · View at Scopus
  13. T. M. McIntyre, A. V. Pontsler, A. R. Silva et al., “Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARγ agonist,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 1, pp. 131–136, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. F. J. Schopfer, Y. Lin, P. R. S. Baker et al., “Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor γ ligand,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 7, pp. 2340–2345, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. S. B. Shappell, R. A. Gupta, S. Manning et al., “15S-hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor γ and inhibits proliferation in PC3 prostate carcinoma cells,” Cancer Research, vol. 61, no. 2, pp. 497–503, 2001. View at Google Scholar · View at Scopus
  16. J. W. F. Elte and J. F. Blicklé, “Thiazolidinediones for the treatment of type 2 diabetes,” European Journal of Internal Medicine, vol. 18, no. 1, pp. 18–25, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. A. Zieleniak, M. Wójcik, and L. A. Woźniak, “Structure and physiological functions of the human peroxisome proliferator-activated receptor γ,” Archivum Immunologiae et Therapiae Experimentalis, vol. 56, no. 5, pp. 331–345, 2008. View at Publisher · View at Google Scholar
  18. S. Chintharlapalli, S. Papineni, M. Konopleva, M. Andreef, I. Samudio, and S. Safe, “2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid and related compounds inhibit growth of colon cancer cells through peroxisome proliferator-activated receptor γ-dependent and -independent pathways,” Molecular Pharmacology, vol. 68, no. 1, pp. 119–128, 2005. View at Publisher · View at Google Scholar
  19. D. M. Ray, K. M. Morse, S. P. Hilchey et al., “The novel triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) induces apoptosis of human diffuse large B-cell lymphoma cells through a peroxisome proliferator-activated receptor gamma-independent pathway,” Experimental Hematology, vol. 34, no. 9, pp. 1202–1211, 2006. View at Google Scholar · View at Scopus
  20. J. M. Lehmann, L. B. Moore, T. A. Smith-Oliver, W. O. Wilkison, T. M. Willson, and S. A. Kliewer, “An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ),” The Journal of Biological Chemistry, vol. 270, no. 22, pp. 12953–12956, 1995. View at Publisher · View at Google Scholar · View at Scopus
  21. Y. Wang, W. W. Porter, N. Suh et al., “A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor γ,” Molecular Endocrinology, vol. 14, no. 10, pp. 1550–1556, 2000. View at Google Scholar · View at Scopus
  22. H. A. Burgess, L. E. Daugherty, T. H. Thatcher et al., “PPARγ agonists inhibit TGF-β induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis,” American Journal of Physiology, vol. 288, no. 6, pp. L1146–L1153, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. A. A. Kulkarni, T. H. Thatcher, K. C. Olsen, S. B. Maggirwar, R. P. Phipps, and P. J. Sime, “PPAR-γ ligands repress TGFβ-induced myofibroblast differentiation by targeting the PI3K/Akt pathway: implications for therapy of fibrosis,” PLoS ONE, vol. 6, no. 1, article e15909, 2011. View at Publisher · View at Google Scholar
  24. S. E. Feldon, C. W. O'Loughlin, D. M. Ray, S. Landskroner-Eiger, K. E. Seweryniak, and R. P. Phipps, “Activated human T lymphocytes express cyclooxygenase-2 and produce proadipogenic prostaglandins that drive human orbital fibroblast differentiation to adipocytes,” American Journal of Pathology, vol. 169, no. 4, pp. 1183–1193, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. B. M. Forman, P. Tontonoz, J. Chen, R. P. Brun, B. M. Spiegelman, and R. M. Evans, “15-deoxy-Δ, -prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ,” Cell, vol. 83, no. 5, pp. 803–812, 1995. View at Google Scholar · View at Scopus
  26. H. E. Ferguson, A. Kulkarni, G. M. Lehmann et al., “Electrophilic peroxisome proliferator-activated receptor-γ ligands have potent antifibrotic effects in human lung fibroblasts,” American Journal of Respiratory Cell and Molecular Biology, vol. 41, no. 6, pp. 722–730, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. H. E. Ferguson, T. H. Thatcher, K. C. Olsen et al., “Peroxisome proliferator-activated receptor-γ ligands induce heme oxygenase-1 in lung fibroblasts by a PPARγ-independent, glutathione-dependent mechanism,” American Journal of Physiology, vol. 297, no. 5, pp. L912–L919, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. B. Melichar, M. Konopleva, W. Hu, K. Melicharova, M. Andreeff, and R. S. Freedman, “Growth-inhibitory effect of a novel synthetic triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, on ovarian carcinoma cell lines not dependent on peroxisome proliferator-activated receptor-γ expression,” Gynecologic Oncology, vol. 93, no. 1, pp. 149–154, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. B. Shi and M. F. Greaney, “Reversible Michael addition of thiols as a new tool for dynamic combinatorial chemistry,” Chemical Communications, no. 7, pp. 886–888, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. N. Suh, Y. Wang, T. Honda et al., “A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9- dien-28-oic acid, with potent differentiating, antiproliferative, and anti- inflammatory activity,” Cancer Research, vol. 59, no. 2, pp. 336–341, 1999. View at Google Scholar · View at Scopus
  31. M. Jordana, B. Sarnstrand, P. J. Sime, and I. Ramis, “Immune-inflammatory functions of fibroblasts,” European Respiratory Journal, vol. 7, no. 12, pp. 2212–2222, 1994. View at Publisher · View at Google Scholar · View at Scopus
  32. K. M. A. O'Reilly, R. P. Phipps, T. H. Thatcher, B. A. Graf, J. Van Kirk, and P. J. Sime, “Crystalline and amorphous silica differentially regulate the cyclooxygenase-prostaglandin pathway in pulmonary fibroblasts: Implications for pulmonary fibrosis,” American Journal of Physiology, vol. 288, no. 6, pp. L1010–L1016, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. M. A. Olman, K. E. White, L. B. Ware et al., “Pulmonary edema fluid from patients with early lung injury stimulates fibroblast proliferation through IL-1β-induced IL-6 expression,” Journal of Immunology, vol. 172, no. 4, pp. 2668–2677, 2004. View at Google Scholar
  34. R. S. Smith, T. J. Smith, T. M. Blieden, and R. P. Phipps, “Fibroblasts as sentinel cells. Synthesis of chemokines and regulation of inflammation,” The American Journal of Pathology, vol. 151, no. 2, pp. 317–322, 1997. View at Google Scholar · View at Scopus
  35. K. M. Fries, G. D. Sempowski, A. A. Gaspari, T. Blieden, R. J. Looney, and R. P. Phipps, “CD40 expression by human fibroblasts,” Clinical Immunology and Immunopathology, vol. 77, no. 1, pp. 42–51, 1995. View at Google Scholar · View at Scopus
  36. C. J. Baglole, S. Y. Reddy, S. J. Pollock et al., “Isolation and phenotypic characterization of lung fibroblasts,” Methods in Molecular Medicine, vol. 117, pp. 115–127, 2005. View at Google Scholar · View at Scopus
  37. T. Mosmann, “Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays,” Journal of Immunological Methods, vol. 65, no. 1-2, pp. 55–63, 1983. View at Google Scholar
  38. L. Koumas, T. J. Smith, and R. P. Phipps, “Fibroblast subsets in the human orbit: thy-1 and Thy-1 subpopulations exhibit distinct phenotypes,” European Journal of Immunology, vol. 32, no. 2, pp. 477–485, 2002. View at Google Scholar · View at Scopus
  39. S. Giri, R. Rattan, A. K. Singh, and I. Singh, “The 15-deoxy-δ12,14-prostaglandin J2 inhibits the inflammatory response in primary rat astrocytes via down-regulating multiple steps in phosphatidylinositol 3-kinase-akt-NF-κB-p300 pathway independent of peroxisome proliferator-activated receptor γ,” Journal of Immunology, vol. 173, no. 8, pp. 5196–5208, 2004. View at Google Scholar · View at Scopus
  40. J. Atsmon, B. J. Sweetman, S. W. Baertschi, T. M. Harris, and L. J. Roberts, “Formation of thiol conjugates of 9-deoxy-delta 9,delta 12(E)-prostaglandin D2 and delta 12(E)-prostaglandin D2,” Biochemistry, vol. 29, pp. 3760–3765, 1990. View at Google Scholar
  41. T. Shibata, T. Yamada, T. Ishii et al., “Thioredoxin as a molecular target of cyclopentenone prostaglandins,” The Journal of Biological Chemistry, vol. 278, no. 28, pp. 26046–26054, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. K. Asada, S. Sasaki, T. Suda, K. Chida, and H. Nakamura, “Antiinflammatory roles of peroxisome proliferator-activated receptor γ in human alveolar macrophages,” American Journal of Respiratory and Critical Care Medicine, vol. 169, no. 2, pp. 195–200, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Kaufman, B. A. Graf, E. C. Leung et al., “Fibroblasts as sentinel cells: role of the CD40-CD40 ligand system in fibroblast activation and lung inflammation and fibrosis,” Chest, vol. 120, no. 1, supplement, pp. S53–S55, 2001. View at Publisher · View at Google Scholar · View at Scopus
  44. L. Koumas, A. E. King, H. O. D. Critchley, R. W. Kelly, and R. P. Phipps, “Fibroblast heterogeneity: existence of functionally distinct Thy 1+ and Thy 1 human female reproductive tract fibroblasts,” American Journal of Pathology, vol. 159, no. 3, pp. 925–935, 2001. View at Google Scholar · View at Scopus
  45. R. A. Derlacz, K. Hyc, M. Usarek, A. K. Jagielski, J. Drozak, and R. Jarzyna, “PPAR-γ-independent inhibitory effect of rosiglitazone on glucose synthesis in primary cultured rabbit kidney-cortex tubules,” Biochemistry and Cell Biology, vol. 86, no. 5, pp. 396–404, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. L. M. Leesnitzer, D. J. Parks, R. K. Bledsoe et al., “Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662,” Biochemistry, vol. 41, no. 21, pp. 6640–6650, 2002. View at Publisher · View at Google Scholar · View at Scopus
  47. A. C. Bendixen, N. K. Shevde, K. M. Dienger, T. M. Willson, C. D. Funk, and J. W. Pike, “IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor γ1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 5, pp. 2443–2448, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. T. Miyahara, L. Schrum, R. Rippe et al., “Peroxisome proliferator-activated receptors and hepatic stellate cell activation,” The Journal of Biological Chemistry, vol. 275, no. 46, pp. 35715–35722, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. J. U. Scher and M. H. Pillinger, “The anti-inflammatory effects of prostaglandins,” Journal of Investigative Medicine, vol. 57, no. 6, pp. 703–708, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. D. S. Straus, G. Pascual, M. Li et al., “15-Deoxy-Δ-prostaglandin J2 inhibits multiple steps in the NF-κB signaling pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 9, pp. 4844–4849, 2000. View at Google Scholar · View at Scopus
  51. H. R. Kim, S. Kim, E. J. Kim et al., “Suppression of Nrf2-driven heme oxygenase-1 enhances the chemosensitivity of lung cancer A549 cells toward cisplatin,” Lung Cancer, vol. 60, no. 1, pp. 47–56, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. T. E. Sussan, T. Rangasamy, D. J. Blake et al., “Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 1, pp. 250–255, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. C. J. Baglole, P. J. Sime, and R. P. Phipps, “Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione,” American Journal of Physiology, vol. 295, no. 4, pp. L624–L636, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. C. Viedt, J. Vogel, T. Athanasiou et al., “Monocyte chemoattractant protein-1 induces proliferation and interleukin-6 production in human smooth muscle cells by differential activation of nuclear factor-κB and activator protein-1,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 22, no. 6, pp. 914–920, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Jacob, R. Wu, M. Zhou, and P. Wang, “Mechanism of the anti-inflammatory effect of curcumin: PPAR-γ activation,” PPAR Research, Article ID 89369, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Nakajima, K. Wada, H. Miki et al., “Endogenous PPARγ mediates anti-inflammatory activity in murine ischemia-reperfusion injury,” Gastroenterology, vol. 120, no. 2, pp. 460–469, 2001. View at Google Scholar · View at Scopus
  57. M. D. Rollins, S. Sudarshan, M. A. Firpo et al., “Anti-inflammatory effects of PPAR-γ agonists directly correlate with PPAR-γ expression during acute pancreatitis,” Journal of Gastrointestinal Surgery, vol. 10, no. 8, pp. 1120–1130, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. P. S. Chaggar, S. M. Shaw, and S. G. Williams, “Review article: thiazolidinediones and heart failure,” Diabetes & Vascular Disease Research, vol. 6, no. 3, pp. 146–152, 2009. View at Google Scholar
  59. C. V. Rizos, M. S. Elisaf, D. P. Mikhailidis, and E. N. Liberopoulos, “How safe is the use of thiazolidinediones in clinical practice?” Expert Opinion on Drug Safety, vol. 8, no. 1, pp. 15–32, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. P. Shah and S. Mudaliar, “Pioglitazone: side effect and safety profile,” Expert Opinion on Drug Safety, vol. 9, no. 2, pp. 347–354, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. C. Giaginis, A. Giagini, and S. Theocharis, “Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands as potential therapeutic agents to treat arthritis,” Pharmacological Research, vol. 60, no. 3, pp. 160–169, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. W. K. Jung, I. S. Park, S. J. Park et al., “The 15-Deoxy-Δ-prostaglandin J2 inhibits LPS-stimulated AKT and NF-κB activation and suppresses interleukin-6 in osteoblast-like cells MC3T3E-1,” Life Sciences, vol. 85, no. 1-2, pp. 46–53, 2009. View at Publisher · View at Google Scholar · View at Scopus