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Peroxisome proliferator-activated receptor gamma activation alleviates postoperative ileus in mice by inhibition of Egr-1 expression and its downstream target genes

OLE DE BACKER UGent, Ellen Elinck UGent, Evelien Priem UGent, Luc Leybaert UGent and Romain Lefebvre UGent (2009) JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 331(2). p.496-503
abstract
Postoperative ileus, a major cause of morbidity after abdominal surgery, is characterized by intestinal dysmotility and a complex inflammatory cascade within the intestinal muscularis. Treatment with carbon monoxide (CO)-inhaled or intraperitoneal-has been shown to ameliorate bowel dysmotility caused by surgical manipulation of the gut in experimental animals. Recent evidence indicates that CO exerts its anti-inflammatory effects through the induction of peroxisome proliferator-activated receptor (PPAR)-gamma, a nuclear receptor whose activation has been linked to several physiological pathways, including those related to the regulation of intestinal inflammation. The purpose of this study was to evaluate pharmacological activation of PPAR gamma in a murine model of postoperative ileus by use of the PPAR gamma agonist rosiglitazone. Postoperative bowel dysmotility was induced by surgical manipulation of the colon. The functional severity of postoperative ileus was significantly ameliorated in mice pretreated with rosiglitazone (0.3 to 10 mg/kg i.p.); this was associated with a down-regulation of pro-inflammatory cytokines/chemokines, inducible nitric oxide synthase activity, cyclooxygenase-2 activity, as well as a decrease in leukocyte recruitment into the muscularis of both colon and jejunum. These anti-inflammatory effects were preceded by a PPAR gamma-dependent down-regulation of early growth response (Egr)-1, a key regulator of inflammatory gene expression. In conclusion, these results indicate that rosiglitazone significantly attenuates postoperative ileus in mice by suppression of the muscularis inflammatory cascade through a PPAR gamma-dependent down-regulation of Egr-1 and encourage the further clinical evaluation of synthetic PPAR gamma agonists as pharmacological tool to prevent this postoperative event.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
J. Pharmacol. Exp. Ther.
volume
331
issue
2
pages
496 - 503
Web of Science type
Article
Web of Science id
000271006200016
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
4.093 (2009)
JCR rank
37/236 (2009)
JCR quartile
1 (2009)
ISSN
0022-3565
DOI
10.1124/jpet.109.155135
language
English
UGent publication?
yes
classification
A1
id
837679
handle
http://hdl.handle.net/1854/LU-837679
date created
2010-01-25 16:46:21
date last changed
2010-01-29 13:47:05
@article{837679,
  abstract     = {Postoperative ileus, a major cause of morbidity after abdominal surgery, is characterized by intestinal dysmotility and a complex inflammatory cascade within the intestinal muscularis. Treatment with carbon monoxide (CO)-inhaled or intraperitoneal-has been shown to ameliorate bowel dysmotility caused by surgical manipulation of the gut in experimental animals. Recent evidence indicates that CO exerts its anti-inflammatory effects through the induction of peroxisome proliferator-activated receptor (PPAR)-gamma, a nuclear receptor whose activation has been linked to several physiological pathways, including those related to the regulation of intestinal inflammation. The purpose of this study was to evaluate pharmacological activation of PPAR gamma in a murine model of postoperative ileus by use of the PPAR gamma agonist rosiglitazone. Postoperative bowel dysmotility was induced by surgical manipulation of the colon. The functional severity of postoperative ileus was significantly ameliorated in mice pretreated with rosiglitazone (0.3 to 10 mg/kg i.p.); this was associated with a down-regulation of pro-inflammatory cytokines/chemokines, inducible nitric oxide synthase activity, cyclooxygenase-2 activity, as well as a decrease in leukocyte recruitment into the muscularis of both colon and jejunum. These anti-inflammatory effects were preceded by a PPAR gamma-dependent down-regulation of early growth response (Egr)-1, a key regulator of inflammatory gene expression. In conclusion, these results indicate that rosiglitazone significantly attenuates postoperative ileus in mice by suppression of the muscularis inflammatory cascade through a PPAR gamma-dependent down-regulation of Egr-1 and encourage the further clinical evaluation of synthetic PPAR gamma agonists as pharmacological tool to prevent this postoperative event.},
  author       = {DE BACKER, OLE and Elinck, Ellen and Priem, Evelien and Leybaert, Luc and Lefebvre, Romain},
  issn         = {0022-3565},
  journal      = {JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS},
  language     = {eng},
  number       = {2},
  pages        = {496--503},
  title        = {Peroxisome proliferator-activated receptor gamma activation alleviates postoperative ileus in mice by inhibition of Egr-1 expression and its downstream target genes},
  url          = {http://dx.doi.org/10.1124/jpet.109.155135},
  volume       = {331},
  year         = {2009},
}

Chicago
DE BACKER, OLE, Ellen Elinck, Evelien Priem, Luc Leybaert, and Romain Lefebvre. 2009. “Peroxisome Proliferator-activated Receptor Gamma Activation Alleviates Postoperative Ileus in Mice by Inhibition of Egr-1 Expression and Its Downstream Target Genes.” Journal of Pharmacology and Experimental Therapeutics 331 (2): 496–503.
APA
DE BACKER, O., Elinck, E., Priem, E., Leybaert, L., & Lefebvre, R. (2009). Peroxisome proliferator-activated receptor gamma activation alleviates postoperative ileus in mice by inhibition of Egr-1 expression and its downstream target genes. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 331(2), 496–503.
Vancouver
1.
DE BACKER O, Elinck E, Priem E, Leybaert L, Lefebvre R. Peroxisome proliferator-activated receptor gamma activation alleviates postoperative ileus in mice by inhibition of Egr-1 expression and its downstream target genes. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 2009;331(2):496–503.
MLA
DE BACKER, OLE, Ellen Elinck, Evelien Priem, et al. “Peroxisome Proliferator-activated Receptor Gamma Activation Alleviates Postoperative Ileus in Mice by Inhibition of Egr-1 Expression and Its Downstream Target Genes.” JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 331.2 (2009): 496–503. Print.