Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2008 (2008), Article ID 148687, 8 pages
http://dx.doi.org/10.1155/2008/148687
Review Article

Pathophysiological Roles of PPAR 𝜸 in Gastrointestinal Epithelial Cells

Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA

Received 28 March 2008; Accepted 19 May 2008

Academic Editor: Dipak Panigrahy

Copyright © 2008 Brian M. Necela and E. Aubrey Thompson. 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. J. Auwerx, “PPARγ, the ultimate thrifty gene,” Diabetologia, vol. 42, no. 9, pp. 1033–1049, 1999. View at Publisher · View at Google Scholar
  2. 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
  3. L. Fajas, D. Auboeuf, E. Raspé et al., “The organization, promoter analysis, and expression of the human PPAR? gene,” The Journal of Biological Chemistry, vol. 272, no. 30, pp. 18779–18789, 1997. View at Publisher · View at Google Scholar
  4. R. Mukherjee, L. Jow, G. E. Croston, and J. R. Paterniti Jr., “Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARγ2 versus PPARγ1 and activation with retinoid X receptor agonists and antagonists,” The Journal of Biological Chemistry, vol. 272, no. 12, pp. 8071–8076, 1997. View at Google Scholar
  5. W. Su, C. R. Bush, B. M. Necela et al., “Differential expression, distribution, and function of PPAR-? in the proximal and distal colon,” Physiological Genomics, vol. 30, no. 3, pp. 342–353, 2007. View at Publisher · View at Google Scholar
  6. A.-M. Lefebvre, B. Paulweber, L. Fajas et al., “Peroxisome proliferator-activated receptor gamma is induced during differentiation of colon epithelium cells,” Journal of Endocrinology, vol. 162, no. 3, pp. 331–340, 1999. View at Publisher · View at Google Scholar
  7. G. D. Girnun and B. M. Spiegelman, “PPARγ ligands: taking Ppart in chemoprevention,” Gastroenterology, vol. 124, no. 2, pp. 564–567, 2003. View at Publisher · View at Google Scholar
  8. L. Chen, C. R. Bush, B. M. Necela et al., “RS5444, a novel PPAR? agonist, regulates aspects of the differentiated phenotype in nontransformed intestinal epithelial cells,” Molecular and Cellular Endocrinology, vol. 251, no. 1-2, pp. 17–32, 2006. View at Publisher · View at Google Scholar
  9. C. R. Bush, J. M. Havens, B. M. Necela et al., “Functional genomic analysis reveals cross-talk between peroxisome proliferator-activated receptor ? and calcium signaling in human colorectal cancer cells,” The Journal of Biological Chemistry, vol. 282, no. 32, pp. 23387–23401, 2007. View at Publisher · View at Google Scholar
  10. S. Drori, G. D. Girnun, L. Tou et al., “Hic-5 regulates an epithelial program mediated by PPAR?,” Genes & Development, vol. 19, no. 3, pp. 362–375, 2005. View at Publisher · View at Google Scholar
  11. L. Chen, B. M. Necela, W. Su et al., “Peroxisome proliferator-activated receptor ? promotes epithelial to mesenchymal transformation by Rho GTPase-dependent activation of ERK1/2,” The Journal of Biological Chemistry, vol. 281, no. 34, pp. 24575–24587, 2006. View at Publisher · View at Google Scholar
  12. P. Tontonoz, E. Hu, R. A. Graves, A. I. Budavari, and B. M. Spiegelman, “mPPARγ2: tissue-specific regulator of an adipocyte enhancer,” Genes & Development, vol. 8, no. 10, pp. 1224–1234, 1994. View at Publisher · View at Google Scholar
  13. P. Tontonoz, E. Hu, and B. M. Spiegelman, “Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor,” Cell, vol. 79, no. 7, pp. 1147–1156, 1994. View at Publisher · View at Google Scholar
  14. E.-Z. Amri, F. Bonino, G. Ailhaud, N. A. Abumrad, and P. A. Grimaldi, “Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors,” The Journal of Biological Chemistry, vol. 270, no. 5, pp. 2367–2371, 1995. View at Publisher · View at Google Scholar
  15. E. Hu, P. Tontonoz, and B. M. Spiegelman, “Transdifferentiation of myoblasts by the adipogenic transcription factors PPARγ and C/EBPα,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 21, pp. 9856–9860, 1995. View at Publisher · View at Google Scholar
  16. P. Tontonoz, E. Hu, J. Devine, E. G. Beale, and B. M. Spiegelman, “PPARγ2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene,” Molecular and Cellular Biology, vol. 15, no. 1, pp. 351–357, 1995. View at Google Scholar
  17. H. Kohno, S. Yoshitani, S. Takashima et al., “Troglitazone, a ligand for peroxisome proliferator-activated receptor ?, inhibits chemically-induced aberrant crypt foci in rats,” Japanese Journal of Cancer Research, vol. 92, no. 4, pp. 396–403, 2001. View at Google Scholar
  18. T. Tanaka, H. Kohno, S. Yoshitani et al., “Ligands for peroxisome proliferator-activated receptors a and ? inhibit chemically induced colitis and formation of aberrant crypt foci in rats,” Cancer Research, vol. 61, no. 6, pp. 2424–2428, 2001. View at Google Scholar
  19. E. Osawa, A. Nakajima, K. Wada et al., “Peroxisome proliferator-activated receptor ? ligands suppress colon carcinogenesis induced by azoxymethane in mice,” Gastroenterology, vol. 124, no. 2, pp. 361–367, 2003. View at Publisher · View at Google Scholar
  20. W. Su, B. M. Necela, K. Fujiwara et al., “The high affinity peroxisome proliferator-activated receptor-gamma agonist RS5444 inhibits both initiation and progression of colon tumors in azoxymethane-treated mice,” International Journal of Cancer, vol. 123, no. 5, pp. 991–997, 2008. View at Publisher · View at Google Scholar
  21. K. Yang, K.-H. Fan, S. A. Lamprecht et al., “Peroxisome proliferator-activated receptor ? agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc1638N/+Mh1+/- double mutant mice,” International Journal of Cancer, vol. 116, no. 4, pp. 495–499, 2005. View at Publisher · View at Google Scholar
  22. M. V. Pino, M. F. Kelley, and Z. Jayyosi, “Promotion of colon tumors in C57BL/6J-APCmin/+ mice by thiazolidinedione PPARγ agonists and a structurally unrelated PPARγ agonist,” Toxicologic Pathology, vol. 32, no. 1, pp. 58–63, 2004. View at Publisher · View at Google Scholar
  23. E. Saez, P. Tontonoz, M. C. Nelson et al., “Activators of the nuclear receptor PPAR? enhance colon polyp formation,” Nature Medicine, vol. 4, no. 9, pp. 1058–1061, 1998. View at Publisher · View at Google Scholar
  24. A.-M. Lefebvre, I. Chen, P. Desreumaux et al., “Activation of the peroxisome proliferator-activated receptor ? promotes the development of colon tumors in C57BL/6J-APCMin/+ mice,” Nature Medicine, vol. 4, no. 9, pp. 1053–1057, 1998. View at Publisher · View at Google Scholar
  25. N. Niho, M. Takahashi, T. Kitamura et al., “Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by peroxisome proliferator-activated receptor ligands,” Cancer Research, vol. 63, no. 18, pp. 6090–6095, 2003. View at Google Scholar
  26. N. Niho, M. Takahashi, Y. Shoji et al., “Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPAR? ligand,” Cancer Science, vol. 94, no. 11, pp. 960–964, 2003. View at Publisher · View at Google Scholar
  27. C. A. McAlpine, Y. Barak, I. Matise, and R. T. Cormier, “Intestinal-specific PPARγ deficiency enhances tumorigenesis in ApcMin/+ mice,” International Journal of Cancer, vol. 119, no. 10, pp. 2339–2346, 2006. View at Publisher · View at Google Scholar
  28. M. Takahashi, S. Nakatsugi, T. Sugimura, and K. Wakabayashi, “Frequent mutations of the β-catenin gene in mouse colon tumors induced by azoxymethane,” Carcinogenesis, vol. 21, no. 6, pp. 1117–1120, 2000. View at Publisher · View at Google Scholar
  29. T. Yoshizumi, T. Ohta, I. Ninomiya et al., “Thiazolidinedione, a peroxisome proliferator-activated receptor-gamma ligand, inhibits growth and metastasis of HT-29 human colon cancer cells through differentiation-promoting effects,” International Journal of Oncology, vol. 25, no. 3, pp. 631–639, 2004. View at Google Scholar
  30. J. A. Brockman, R. A. Gupta, and R. N. DuBois, “Activation of PPARγ leads to inhibition of anchorage-independent growth of human colorectal cancer cells,” Gastroenterology, vol. 115, no. 5, pp. 1049–1055, 1998. View at Publisher · View at Google Scholar
  31. G. G. Chen, J. F. Lee, S. H. Wang, U. P. F. Chan, P. C. Ip, and W. Y. Lau, “Apoptosis induced by activation of peroxisome-proliferator activated receptor-gamma is associated with Bcl-2 and Nf-κB in human colon cancer,” Life Sciences, vol. 70, no. 22, pp. 2631–2646, 2002. View at Publisher · View at Google Scholar
  32. R. A. Gupta, P. Sarraf, J. A. Brockman et al., “Peroxisome proliferator-activated receptor ? and transforming growth factor-ß pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22,” The Journal of Biological Chemistry, vol. 278, no. 9, pp. 7431–7438, 2003. View at Publisher · View at Google Scholar
  33. S. Kitamura, Y. Miyazaki, Y. Shinomura, S. Kondo, S. Kanayama, and Y. Matsuzawa, “Peroxisome proliferator-activated receptor γ induces growth arrest and differentiation markers of human colon cancer cells,” Japanese Journal of Cancer Research, vol. 90, no. 1, pp. 75–80, 1999. View at Google Scholar
  34. P. Sarraf, E. Mueller, D. Jones et al., “Differentiation and reversal of malignant changes in colon cancer through PPAR?,” Nature Medicine, vol. 4, no. 9, pp. 1046–1052, 1998. View at Publisher · View at Google Scholar
  35. T. Shimada, K. Kojima, K. Yoshiura, H. Hiraishi, and A. Terano, “Characteristics of the peroxisome proliferator activated receptor γ (PPARγ) ligand induced apoptosis in colon cancer cells,” Gut, vol. 50, no. 5, pp. 658–664, 2002. View at Publisher · View at Google Scholar
  36. P. Sarraf, E. Mueller, W. M. Smith et al., “Loss-of-function mutations in PPAR? associated with human colon cancer,” Molecular Cell, vol. 3, no. 6, pp. 799–804, 1999. View at Publisher · View at Google Scholar
  37. T. Ikezoe, C. W. Miller, S. Kawano et al., “Mutational analysis of the peroxisome proliferator-activated receptor ? in human malignancies,” Cancer Research, vol. 61, no. 13, pp. 5307–5310, 2001. View at Google Scholar
  38. S. Tomita, H. Kawamata, J. Imura, F. Omotehara, Y. Ueda, and T. Fujimori, “Frequent polymorphism of peroxisome proliferator activated receptor gamma gene in colorectal cancer containing wild-type K-ras gene,” International Journal of Molecular Medicine, vol. 9, no. 5, pp. 485–488, 2002. View at Google Scholar
  39. L. Dubuquoy, E. Å. Jansson, S. Deeb et al., “Impaired expression of peroxisome proliferator-activated receptor ? in ulcerative colitis,” Gastroenterology, vol. 124, no. 5, pp. 1265–1276, 2003. View at Publisher · View at Google Scholar
  40. F. Bogazzi, F. Ultimieri, F. Raggi et al., “Peroxisome proliferator activated receptor ? expression is reduced in the colonic mucosa of acromegalic patients,” The Journal of Clinical Endocrinology & Metabolism, vol. 87, no. 5, pp. 2403–2406, 2002. View at Publisher · View at Google Scholar
  41. G. D. Girnun, W. M. Smith, S. Drori et al., “APC-dependent suppression of colon carcinogenesis by PPAR?,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 21, pp. 13771–13776, 2002. View at Publisher · View at Google Scholar
  42. M. H. Kulke, G. D. Demetri, N. E. Sharpless et al., “A phase II study of troglitazone, an activator of the PPAR? receptor, in patients with chemotherapy-resistant metastatic colorectal cancer,” Cancer Journal, vol. 8, no. 5, pp. 395–399, 2002. View at Publisher · View at Google Scholar
  43. R. A. Gupta, P. Sarraf, E. Mueller et al., “Peroxisome proliferator-activated receptor ?-mediated differentiation: a mutation in colon cancer cells reveals divergent and cell type-specific mechanisms,” The Journal of Biological Chemistry, vol. 278, no. 25, pp. 22669–22677, 2003. View at Publisher · View at Google Scholar
  44. S. E. Nissen and K. Wolski, “Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes,” The New England Journal of Medicine, vol. 356, no. 24, pp. 2457–2471, 2007. View at Publisher · View at Google Scholar
  45. T. Yokota, K. Sugano, H. Kondo et al., “Detection of aberrant crypt foci by magnifying colonoscopy,” Gastrointestinal Endoscopy, vol. 46, no. 1, pp. 61–65, 1997. View at Publisher · View at Google Scholar
  46. T. Takayama, S. Katsuki, Y. Takahashi et al., “Aberrant crypt foci of the colon as precursors of adenoma and cancer,” The New England Journal of Medicine, vol. 339, no. 18, pp. 1277–1284, 1998. View at Publisher · View at Google Scholar
  47. D. G. Adler, C. J. Gostout, D. Sorbi, L. J. Burgart, L. Wang, and W. S. Harmsen, “Endoscopic identification and quantification of aberrant crypt foci in the human colon,” Gastrointestinal Endoscopy, vol. 56, no. 5, pp. 657–662, 2002. View at Publisher · View at Google Scholar
  48. C. Koro, S. Barrett, and N. Qizilbash, “Cancer risks in thiazolidinedione users compared to other anti-diabetic agents,” Pharmacoepidemiology and Drug Safety, vol. 16, no. 5, pp. 485–492, 2007. View at Publisher · View at Google Scholar
  49. C. S. Eun, D. S. Han, S. H. Lee et al., “Attenuation of colonic inflammation by PPAR? in intestinal epithelial cells: effect on toll-like receptor pathway,” Digestive Diseases and Sciences, vol. 51, no. 4, pp. 693–697, 2006. View at Publisher · View at Google Scholar
  50. C. G. Su, X. Wen, S. T. Bailey et al., “A novel therapy for colitis utilizing PPAR-? ligands to inhibit the epithelial inflammatory response,” The Journal of Clinical Investigation, vol. 104, no. 4, pp. 383–389, 1999. View at Publisher · View at Google Scholar
  51. G. Chinetti, S. Griglio, M. Antonucci et al., “Activation of proliferator-activated receptors a and ? induces apoptosis of human monocyte-derived macrophages,” The Journal of Biological Chemistry, vol. 273, no. 40, pp. 25573–25580, 1998. View at Publisher · View at Google Scholar
  52. M. Ricote, J. S. Welch, and C. K. Glass, “Regulation of macrophage gene expression by the peroxisome proliferator-activated receptor-γ,” Hormone Research, vol. 54, no. 5-6, pp. 275–280, 2000. View at Publisher · View at Google Scholar
  53. D. G. Alleva, E. B. Johnson, F. M. Lio, S. A. Boehme, P. J. Conlon, and P. D. Crowe, “Regulation of murine macrophage proinflammatory and anti-inflammatory cytokines by ligands for peroxisome proliferator-activated receptor-γ: counter-regulatory activity by IFN-γ,” Journal of Leukocyte Biology, vol. 71, no. 4, pp. 677–685, 2002. View at Google Scholar
  54. C. Jiang, A. T. Ting, and B. Seed, “PPAR-γ agonists inhibit production of monocyte inflammatory cytokines,” Nature, vol. 391, no. 6662, pp. 82–86, 1998. View at Publisher · View at Google Scholar
  55. V. Angeli, H. Hammad, B. Staels, M. Capron, B. N. Lambrecht, and F. Trottein, “Peroxisome proliferator-activated receptor γ inhibits the migration of dendritic cells: consequences for the immune response,” The Journal of Immunology, vol. 170, no. 10, pp. 5295–5301, 2003. View at Google Scholar
  56. P. Gosset, A.-S. Charbonnier, P. Delerive et al., “Peroxisome proliferator-activated receptor ? activators affect the maturation of human monocyte-derived dendritic cells,” European Journal of Immunology, vol. 31, no. 10, pp. 2857–2865, 2001. View at Publisher · View at Google Scholar
  57. C. Faveeuw, S. Fougeray, V. Angeli et al., “Peroxisome proliferator-activated receptor ? activators inhibit interleukin-12 production in murine dendritic cells,” FEBS Letters, vol. 486, no. 3, pp. 261–266, 2000. View at Publisher · View at Google Scholar
  58. P. W. Thompson, A. I. Bayliffe, A. P. Warren, and J. R. Lamb, “Interleukin-10 is upregulated by nanomolar rosiglitazone treatment of mature dendritic cells and human CD4+ T cells,” Cytokine, vol. 39, no. 3, pp. 184–191, 2007. View at Publisher · View at Google Scholar
  59. M. Soller, S. Dröse, U. Brandt, B. Brüne, and A. von Knethen, “Mechanism of thiazolidinedione-dependent cell death in Jurkat T cells,” Molecular Pharmacology, vol. 71, no. 6, pp. 1535–1544, 2007. View at Publisher · View at Google Scholar
  60. R. B. Clark, D. Bishop-Bailey, T. Estrada-Hernandez, T. Hla, L. Puddington, and S. J. Padula, “The nuclear receptor PPARγ and immunoregulation: PPARγ mediates inhibition of helper T cell responses,” The Journal of Immunology, vol. 164, no. 3, pp. 1364–1371, 2000. View at Google Scholar
  61. K. J. Moore, M. L. Fitzgerald, and M. W. Freeman, “Peroxisome proliferator-activated receptors in macrophage biology: friend or foe?” Current Opinion in Lipidology, vol. 12, no. 5, pp. 519–527, 2001. View at Publisher · View at Google Scholar
  62. A. Chawla, Y. Barak, L. Nagy, D. Liao, P. Tontonoz, and R. M. Evans, “PPAR-γ dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation,” Nature Medicine, vol. 7, no. 1, pp. 48–52, 2001. View at Publisher · View at Google Scholar
  63. M. B. Crosby, J. L. Svenson, J. Zhang, C. J. Nicol, F. J. Gonzalez, and G. S. Gilkeson, “Peroxisome proliferation-activated receptor (PPAR)γ is not necessary for synthetic PPARγ agonist inhibition of inducible nitric-oxide synthase and nitric oxide,” Journal of Pharmacology and Experimental Therapeutics, vol. 312, no. 1, pp. 69–76, 2005. View at Publisher · View at Google Scholar
  64. P. Desreumaux, L. Dubuquoy, S. Nutten et al., “Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor ? (PPAR?) heterodimer: a basis for new therapeutic strategies,” Journal of Experimental Medicine, vol. 193, no. 7, pp. 827–838, 2001. View at Publisher · View at Google Scholar
  65. L. J. Saubermann, A. Nakajima, K. Wada et al., “Peroxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response and prevent acute colitis,” Inflammatory Bowel Diseases, vol. 8, no. 5, pp. 330–339, 2002. View at Publisher · View at Google Scholar
  66. M. Adachi, R. Kurotani, K. Morimura et al., “Peroxisome proliferator activated receptor ? in colonic epithelial cells protects against experimental inflammatory bowel disease,” Gut, vol. 55, no. 8, pp. 1104–1113, 2006. View at Publisher · View at Google Scholar
  67. Y. M. Shah, K. Morimura, and F. J. Gonzalez, “Expression of peroxisome proliferator-activated receptor-γ in macrophage suppresses experimentally induced colitis,” American Journal of Physiology, vol. 292, no. 2, pp. G657–G666, 2007. View at Publisher · View at Google Scholar
  68. F. R. Byrne and J. L. Viney, “Mouse models of inflammatory bowel disease,” Current Opinion in Drug Discovery & Development, vol. 9, no. 2, pp. 207–217, 2006. View at Google Scholar
  69. S. Wirtz and M. F. Neurath, “Mouse models of inflammatory bowel disease,” Advanced Drug Delivery Reviews, vol. 59, no. 11, pp. 1073–1083, 2007. View at Publisher · View at Google Scholar
  70. W. Strober, I. J. Fuss, and R. S. Blumberg, “The immunology of mucosal models of inflammation,” Annual Review of Immunology, vol. 20, pp. 495–549, 2002. View at Publisher · View at Google Scholar
  71. K. L. Schaefer, S. Denevich, C. Ma et al., “Intestinal antiinflammatory effects of thiazolidenedione peroxisome proliferator-activated receptor-? ligands on T helper type 1 chemokine regulation include nontranscriptional control mechanisms,” Inflammatory Bowel Diseases, vol. 11, no. 3, pp. 244–252, 2005. View at Publisher · View at Google Scholar
  72. M. Sánchez-Hidalgo, A. R. Martín, I. Villegas, and C. A. de la Lastra, “Rosiglitazone, a PPARγ ligand, modulates signal transduction pathways during the development of acute TNBS-induced colitis in rats,” European Journal of Pharmacology, vol. 562, no. 3, pp. 247–258, 2007. View at Publisher · View at Google Scholar
  73. K. Katayama, K. Wada, A. Nakajima et al., “A novel PPAR? gene therapy to control inflammation associated with inflammatory bowel disease in a murine model,” Gastroenterology, vol. 124, no. 5, pp. 1315–1324, 2003. View at Publisher · View at Google Scholar
  74. C. Lytle, T. J. Tod, K. T. Vo, J. W. Lee, R. D. Atkinson, and D. S. Straus, “The peroxisome proliferator-activated receptor γ ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency,” Inflammatory Bowel Diseases, vol. 11, no. 3, pp. 231–243, 2005. View at Publisher · View at Google Scholar
  75. J. D. Ramakers, M. I. Verstege, G. Thuijls, A. A. Te Velde, R. P. Mensink, and J. Plat, “The PPARγ agonist rosiglitazone impairs colonic inflammation in mice with experimental colitis,” Journal of Clinical Immunology, vol. 27, no. 3, pp. 275–283, 2007. View at Publisher · View at Google Scholar
  76. J. D. Lewis, G. R. Lichtenstein, R. B. Stein et al., “An open-label trial of the PPAR? ligand rosiglitazone for active ulcerative colitis,” American Journal of Gastroenterology, vol. 96, no. 12, pp. 3323–3328, 2001. View at Publisher · View at Google Scholar
  77. M. Sánchez-Hidalgo, A. R. Martín, I. Villegas, and C. A. de La Lastra, “Rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma, reduces chronic colonic inflammation in rats,” Biochemical Pharmacology, vol. 69, no. 12, pp. 1733–1744, 2005. View at Publisher · View at Google Scholar
  78. K. Takaki, K. Mitsuyama, O. Tsuruta, A. Toyonaga, and M. Sata, “Attenuation of experimental colonic injury by thiazolidinedione agents,” Inflammation Research, vol. 55, no. 1, pp. 10–15, 2006. View at Publisher · View at Google Scholar
  79. J. D. Lewis, G. R. Lichtenstein, J. J. Deren et al., “Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial,” Gastroenterology, vol. 134, no. 3, pp. 688–695, 2008. View at Publisher · View at Google Scholar
  80. B. M. Necela, W. Su, and E. A. Thompson, “Toll-like receptor 4 mediates cross-talk between peroxisome proliferator-activated receptor γ and nuclear factor-κB in macrophages,” Immunology. In press. View at Publisher · View at Google Scholar