Attenuation of acute pancreatitis by peroxisome proliferator-activated receptor-α in rats: the effect on Toll-like receptor signaling pathways.

Abstract

OBJECTIVES:

The peroxisome proliferator-activated receptor-α (PPAR-α) has attracted considerable attention for its anti-inflammatory properties; however, Toll-like receptor (TLR) pathways have an essential proinflammatory role in acute pancreatitis (AP). This study aimed to evaluate the attenuation of inflammation by PPAR-α and to investigate the interaction between PPAR-α and TLR pathways in AP.

METHODS:

Acute pancreatitis was induced in rats by administration of cerulein. The PPAR-α agonist WY14643 and/or antagonist MK886 was administered. The severity of AP was determined by measuring serum amylase, lipase, Ca(2+), pathological changes, myeloperoxidase activity, serum levels of interleukin (IL)-6, and intercellular adhesion molecule-1 (ICAM-1). The TLR2 and TLR4 messenger RNA (mRNA) and proteins were determined by real-time reverse transcriptase polymerase chain reaction and Western blotting, respectively. The mRNA expressions of target molecules of TLR pathways, including IL-6, IL-10, ICAM-1, and tumor necrosis factor α were also measured.

RESULTS:

Treatment with WY14643 significantly decreased amylase, lipase, myeloperoxidase activity, pathological scores, IL-6, and ICAM-1 levels. The TLR2 and TLR4 mRNA and proteins were markedly decreased after treatment with WY14643, along with IL-6, ICAM-1, and tumor necrosis factor α mRNA levels. However, these effects were completely reversed by the coadministration of MK886.

CONCLUSIONS:

Activation of PPAR-α played a protective role in AP, partially mediated by modulation of TLR pathways.

• Authors: Jun-Li Ding, Zong-Guang Zhou, Xiang-Yu Zhou, Bin Zhou, Ling Wang, Rong Wang, Lan Zhan, Xiao-Feng Sun, Yuan Li
• Journal: Pancreas (Pancreas) Vol. 42 Issue 1 Pg. 114-22 (Jan 2013) ISSN: 1536-4828 [Electronic] United States
• PMID: 22722259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Biomarkers
• Cytokines
• Indoles
• PPAR alpha
• Pyrimidines
• RNA, Messenger
• Tlr2 protein, rat
• Tlr4 protein, rat
• Tlr9 protein, rat
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Toll-Like Receptor 9
• Toll-Like Receptors
• MK-886
• Intercellular Adhesion Molecule-1
• pirinixic acid
• Ceruletide
• Peroxidase
• Lipase
• Amylases
• Calcium

Topics

• Amylases (blood)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Biomarkers (blood)
• Blotting, Western
• Calcium (blood)
• Ceruletide
• Cytokines (blood, genetics)
• Disease Models, Animal
• Gene Expression Regulation
• Indoles (pharmacology)
• Intercellular Adhesion Molecule-1 (blood, genetics)
• Lipase (blood)
• Male
• Neutrophil Infiltration (drug effects)
• PPAR alpha (agonists, antagonists & inhibitors, metabolism)
• Pancreas (drug effects, immunology, metabolism)
• Pancreatitis (blood, chemically induced, genetics, immunology, prevention & control)
• Peroxidase (metabolism)
• Pyrimidines (pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Time Factors
• Toll-Like Receptor 2 (drug effects, metabolism)
• Toll-Like Receptor 4 (drug effects, metabolism)
• Toll-Like Receptor 9 (drug effects, metabolism)
• Toll-Like Receptors (drug effects, genetics, metabolism)