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Activated and inactivated PPARs-γ modulate experimentally induced colitis in rats.

Celinski K, Dworzanski T, Korolczuk A, Slomka M, Radej S, Cichoz-Lach H, Madro A - Med. Sci. Monit. (2011)

Bottom Line: Rosiglitazone alone decreased expression of IL-6; used with TNBS it decreased expression of MPO in intestinal tissue, yet did not increase the expression of IL-10.Decreased levels of MPO indicate reduced neutrophil-dependent immune response.Rosiglitazone inhibits expression of proinflammatory IL-6 and does not affect IL-10.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Medical University of Lublin, Lublin, Poland. celinski@mp.pl

ABSTRACT

Background: This study sought to define the mechanism by which PPAR-γ ligands affect the course of experimentally induced colitis in rats.

Material/methods: Inflammation was induced in Wistar rats by a single rectal administration of 2,4,6,-trinitrobenzene sulfonic acid (TNBS). The antagonist of PPARγ antagonist, bisphenol A diglycidyl ether (BADGE), was administrated intraperitoneally 120 mg/kg 4 times every other day. Rosiglitazone 8 mg/kg was administrated by gastric tube 4 times. Body weight was measured daily. After killing, the large intestinal tissue was weighed and collected for histopathologic and immunoenzymatic tests. Levels of IL-6, IL-10, and myeloperoxidase (MPO) were determined in serum and in intestinal homogenates.

Results: Rats receiving rosiglitazone had higher body weight, whereas large intestine weight/length ratio was lower; histology showed fewer inflammatory markers. Rats receiving TNBS and TNBS along with BADGE had more intensive inflammatory changes. Rosiglitazone alone decreased expression of IL-6; used with TNBS it decreased expression of MPO in intestinal tissue, yet did not increase the expression of IL-10. Decreased levels of MPO indicate reduced neutrophil-dependent immune response. The antagonist of PPAR-γ increased IL-6 in serum and decreased IL-10 in intestinal homogenates. Bisphenol A diglycidyl ether administrated to healthy animals increases serum IL-6 levels.

Conclusions: Rosiglitazone inhibits experimental inflammation; administration of its selective antagonist abolishes this protective influence. Rosiglitazone inhibits expression of proinflammatory IL-6 and does not affect IL-10. Agonists of PPARs-γ are possibilities for inflammatory bowel disease prevention. Exogenous substances blocking PPARs-γ may contribute to development or relapse of nonspecific inflammatory bowel diseases.

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Related in: MedlinePlus

Histopathological picture of the large intestine in group IV (TNBS). H+E ×200. Ulcerations of intestinal musoca covered with the fibrin pseudomembrane reaching its muscular lamina, very intensive inflammatory neutrophil infiltration, submucosal oedema.
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f3-medscimonit-17-4-br116: Histopathological picture of the large intestine in group IV (TNBS). H+E ×200. Ulcerations of intestinal musoca covered with the fibrin pseudomembrane reaching its muscular lamina, very intensive inflammatory neutrophil infiltration, submucosal oedema.

Mentions: Transmural inflammatory changes were observed in most parts of the intestinal surface. Marked epithelium necrosis and intestinal wall edema were visualized. Diffuse, intensive, inflammatory infiltration of neutrophils and less-intensive infiltration of mononuclear cells were found within the mucosa, submucosa, and muscular layer. Moreover, crypt abscesses and numerous deep ulcerations, exceeding the muscular lamina, were noted. Slight fibroma within the submucosal layer, local atrophy of crypt structures, and decreased amounts of mucus also were observed. The mucus layer covering the epithelium was lacking (Figure 3).


Activated and inactivated PPARs-γ modulate experimentally induced colitis in rats.

Celinski K, Dworzanski T, Korolczuk A, Slomka M, Radej S, Cichoz-Lach H, Madro A - Med. Sci. Monit. (2011)

Histopathological picture of the large intestine in group IV (TNBS). H+E ×200. Ulcerations of intestinal musoca covered with the fibrin pseudomembrane reaching its muscular lamina, very intensive inflammatory neutrophil infiltration, submucosal oedema.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539512&req=5

f3-medscimonit-17-4-br116: Histopathological picture of the large intestine in group IV (TNBS). H+E ×200. Ulcerations of intestinal musoca covered with the fibrin pseudomembrane reaching its muscular lamina, very intensive inflammatory neutrophil infiltration, submucosal oedema.
Mentions: Transmural inflammatory changes were observed in most parts of the intestinal surface. Marked epithelium necrosis and intestinal wall edema were visualized. Diffuse, intensive, inflammatory infiltration of neutrophils and less-intensive infiltration of mononuclear cells were found within the mucosa, submucosa, and muscular layer. Moreover, crypt abscesses and numerous deep ulcerations, exceeding the muscular lamina, were noted. Slight fibroma within the submucosal layer, local atrophy of crypt structures, and decreased amounts of mucus also were observed. The mucus layer covering the epithelium was lacking (Figure 3).

Bottom Line: Rosiglitazone alone decreased expression of IL-6; used with TNBS it decreased expression of MPO in intestinal tissue, yet did not increase the expression of IL-10.Decreased levels of MPO indicate reduced neutrophil-dependent immune response.Rosiglitazone inhibits expression of proinflammatory IL-6 and does not affect IL-10.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Medical University of Lublin, Lublin, Poland. celinski@mp.pl

ABSTRACT

Background: This study sought to define the mechanism by which PPAR-γ ligands affect the course of experimentally induced colitis in rats.

Material/methods: Inflammation was induced in Wistar rats by a single rectal administration of 2,4,6,-trinitrobenzene sulfonic acid (TNBS). The antagonist of PPARγ antagonist, bisphenol A diglycidyl ether (BADGE), was administrated intraperitoneally 120 mg/kg 4 times every other day. Rosiglitazone 8 mg/kg was administrated by gastric tube 4 times. Body weight was measured daily. After killing, the large intestinal tissue was weighed and collected for histopathologic and immunoenzymatic tests. Levels of IL-6, IL-10, and myeloperoxidase (MPO) were determined in serum and in intestinal homogenates.

Results: Rats receiving rosiglitazone had higher body weight, whereas large intestine weight/length ratio was lower; histology showed fewer inflammatory markers. Rats receiving TNBS and TNBS along with BADGE had more intensive inflammatory changes. Rosiglitazone alone decreased expression of IL-6; used with TNBS it decreased expression of MPO in intestinal tissue, yet did not increase the expression of IL-10. Decreased levels of MPO indicate reduced neutrophil-dependent immune response. The antagonist of PPAR-γ increased IL-6 in serum and decreased IL-10 in intestinal homogenates. Bisphenol A diglycidyl ether administrated to healthy animals increases serum IL-6 levels.

Conclusions: Rosiglitazone inhibits experimental inflammation; administration of its selective antagonist abolishes this protective influence. Rosiglitazone inhibits expression of proinflammatory IL-6 and does not affect IL-10. Agonists of PPARs-γ are possibilities for inflammatory bowel disease prevention. Exogenous substances blocking PPARs-γ may contribute to development or relapse of nonspecific inflammatory bowel diseases.

Show MeSH
Related in: MedlinePlus