Volume 132, Issue 5, Pages (May 2007)

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Volume 132, Issue 5, Pages 1791-1803 (May 2007) The Role of PPARγ on Restoration of Colonic Homeostasis After Experimental Stress- Induced Inflammation and Dysfunction  Ángel Ponferrada, Javier R. Caso, Luis Alou, Arturo Colón, David Sevillano, María A. Moro, Ignacio Lizasoain, Pedro Menchén, María L. Gómez–Lus, Pedro Lorenzo, Enrique Cos, Juan C. Leza, Luis Menchén  Gastroenterology  Volume 132, Issue 5, Pages 1791-1803 (May 2007) DOI: 10.1053/j.gastro.2007.02.032 Copyright © 2007 AGA Institute Terms and Conditions

Figure 1 (A) Effect of immobilization stress during 6 hours, 5 days, and 10 days on weight of rats receiving vehicle (saline), rosiglitazone (3 mg/kg), or 15d-PGJ2 (120 μg/kg) at the onset of each stress session. The data represent the mean ± SEM of 8 rats. *P < .05 vs control nonstressed animals; #,†P < .05 vs saline. (B) Effect of immobilization stress during 6 hours, 5 days, and 10 days on colonic MPO activity of rats receiving vehicle (saline), rosiglitazone (3 mg/kg), or 15d-PGJ2 (120 μg/kg) at the onset of each stress session. The data represent the mean ± SEM of 8 rats. *P < .05 vs control nonstressed animals; #,†P < .05 vs saline. Gastroenterology 2007 132, 1791-1803DOI: (10.1053/j.gastro.2007.02.032) Copyright © 2007 AGA Institute Terms and Conditions

Figure 2 (A) COX-2 and NOS-2 protein expression in colon from control and stressed rats for 6 hours, 5 days, and 10 days. Effect of rosiglitazone (3 mg/kg) and 15d-PGJ2 (120 μg/kg) treatment. Data are representative of 3 animals. (B) Densitometric analysis of COX-2 protein (n = 3); mean density was calculated, plotted, and compared for statistical significance. (C) Densitometric analysis of NOS-2 protein (n = 3). *,#P < .05 vs correspondent saline injected animals exposed to immobilization stress. (D) Effect of immobilization stress during 6 hours, 5 days, and 10 days on colonic PGE2 production of rats receiving vehicle (saline), rosiglitazone (3 mg/kg), or 15d-PGJ2 (120 μg/kg) at the onset of each stress session. The data represent the mean ± SEM of 8 rats. *P < .05 vs control nonstressed animals; #,†P < .05 vs saline. Gastroenterology 2007 132, 1791-1803DOI: (10.1053/j.gastro.2007.02.032) Copyright © 2007 AGA Institute Terms and Conditions

Figure 3 Analysis of COX-1 and NOS-1 protein expression by Western blot in colon from control and stressed rats for 6 hours, 5 days, and 10 days. Data are representative of 3 animals. Gastroenterology 2007 132, 1791-1803DOI: (10.1053/j.gastro.2007.02.032) Copyright © 2007 AGA Institute Terms and Conditions

Figure 4 (A) Effect of immobilization stress during 6 hours, 5 days, and 10 days on colonic 15d-PGJ2 production of rats receiving vehicle (saline), rosiglitazone (3 mg/kg), or 15d-PGJ2 (120 μg/kg) at the onset of each stress session. The data represent the mean ± SEM of 8 rats. *P < .05 vs control nonstressed animals; #,†P < .05 vs saline. (B) Analysis of PPARγ expression by Western blot in colon from control and stressed rats for 6 hours, 5 days, and 10 days. Data are representative of 3 animals. Gastroenterology 2007 132, 1791-1803DOI: (10.1053/j.gastro.2007.02.032) Copyright © 2007 AGA Institute Terms and Conditions

Figure 5 Colonic permeability to 51Cr-EDTA (expressed as the ratio between blood and total 51Cr instilled and reported as a percentage) in rats exposed to immobilization stress during 6 hours, 5 days, and 10 days. Effect of rosiglitazone (3 mg/kg) and 15d-PGJ2 (120 μg/kg) treatment. The data represent the mean ± SEM of 10 rats. *P < .05 vs control nonstressed animals; #,†P < .05 vs saline. (B) Bacterial translocation to mesenteric lymph nodes in rats exposed to immobilization stress during 6 hours, 5 days, and 10 days. Effect of rosiglitazone (3 mg/kg) and 15d-PGJ2 (120 μg/kg) treatment. The data represent the mean ± SEM of 8 rats. *P < .05 vs control nonstressed animals; #P < .05 vs saline. Gastroenterology 2007 132, 1791-1803DOI: (10.1053/j.gastro.2007.02.032) Copyright © 2007 AGA Institute Terms and Conditions

Figure 6 Transmission electron micrographs of the TJ region of colonic epithelial cells from (A) control rats or animals exposed to immobilization stress during (B) 6 hours, (C) 5 days, and (D) 10 days. Immobilization stress for 6 hours and 5 days induced an increased proportion of TJ dilatation and disruption (white arrows) versus control animals (see numerical data in the text). Gastroenterology 2007 132, 1791-1803DOI: (10.1053/j.gastro.2007.02.032) Copyright © 2007 AGA Institute Terms and Conditions

Figure 7 Effect of immobilization stress during 6 hours, 5 days, and 10 days on colonic IgA synthesis of rats receiving vehicle (saline), rosiglitazone (3 mg/kg), or 15d-PGJ2 (120 μg/kg) at the onset of each stress session. The data represent the mean ± SEM of 8 rats. *P < .05 vs control nonstressed animals; #,†P < .05 vs saline. Gastroenterology 2007 132, 1791-1803DOI: (10.1053/j.gastro.2007.02.032) Copyright © 2007 AGA Institute Terms and Conditions

Figure 8 Effect of immobilization stress during 6 hours, 5 days, and 10 days on corticosterone release of rats receiving vehicle (saline), rosiglitazone (3 mg/kg), or 15d-PGJ2 (120 μg/kg) at the onset of each stress session. The data represent the mean ± SEM of 8 rats. *P < .05 vs control nonstressed animals; #,†P = NS vs saline. Gastroenterology 2007 132, 1791-1803DOI: (10.1053/j.gastro.2007.02.032) Copyright © 2007 AGA Institute Terms and Conditions

Figure 9 Effect of immobilization stress during 6 hours on (A) colonic MPO activity, (B) PGE2 production, (C) NOS-2 expression (representative Western blot [inset] and densitometry plot, n = 3), (D) colonic permeability to 51Cr-EDTA, (E) bacterial translocation to mesenteric lymph nodes, and (F) colonic IgA production of rats receiving vehicle (saline), T0070907 (2 mg/kg), rosiglitazone (3 mg/kg), 15d-PGJ2 (120 μg/kg), T0070907 plus rosiglitazone, or T0070907 plus 15d-PGJ2. The data represent the mean ± SEM of 8 rats. *P < .05 vs rosiglitazone-treated animals; #P < .05 vs 15d-PGJ2–treated animals. Gastroenterology 2007 132, 1791-1803DOI: (10.1053/j.gastro.2007.02.032) Copyright © 2007 AGA Institute Terms and Conditions