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Differential anti-inflammatory properties of peroxisome proliferator-activated receptors (PPAR) α and γ in experimental pancreatitis

Perfluorooctanoic acid (PFOA) has anti-inflammatory effects in models of cutaneous inflammation, possibly via activation of PPAR-α and PPAR-γ. We have therefore investigated whether PFOA has similar effects in a model of acute oedematous pancreatitis and whether such effects could be explained by agonism at PPAR-α or PPAR-γ. Acute pancreatitis was induced in anesthetized rats by i.v. infusion of the cholecystokinin analogue, caerulein. The PPAR-α agonist clofibrate or the PPAR-γ agonist rosiglitazone were injected s.c. before the experiments. Pancreatic oedema, neutrophil activation and production of prostaglandin (PG) E2 and prostacyclin (via 6-keto-PGF) were assessed in the pancreas. Acute pancreatitis caused significant oedema formation, neutrophil activation as assessed by myeloperoxidase activity in the tissue, and increased synthesis of pro-inflammatory prostanoids. Neutrophil activation was unaffected by clofibrate but was abolished by rosiglitazone. In contrast, prostanoid synthesis was unaffected by rosiglitazone but was inhibited by clofibrate. In conclusion, our data demonstrate that activation of PPAR-α and PPAR-γ has differential anti-inflammatory effects in acute interstitial-oedematous pancreatitis. Neutrophil activation is sensitive to inhibition by PPAR-γ activation while the production of pro-inflammatory prostanoids can be attenuated by activation of PPAR-α. Thus, the anti-inflammatory potential of PPAR-α and PPAR-γ ligands should be further investigated.

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Correspondence to Thomas Griesbacher.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Griesbacher, T., Pommer, V., Schuligoi, R. et al. Differential anti-inflammatory properties of peroxisome proliferator-activated receptors (PPAR) α and γ in experimental pancreatitis. BMC Pharmacol 7, A20 (2007). https://doi.org/10.1186/1471-2210-7-S2-A20

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  • DOI: https://doi.org/10.1186/1471-2210-7-S2-A20

Keywords

  • Pancreatitis
  • Acute Pancreatitis
  • Rosiglitazone
  • Cholecystokinin
  • Clofibrate