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Attenuation of Acute Pancreatitis by Peroxisome Proliferator-Activated Receptor-α in Rats: The Effect on Toll-Like Receptor Signaling Pathways
Sichuan University, Peoples R China .
Sichuan University, Peoples R China .
Sichuan University, Peoples R China .
Sichuan University, Peoples R China .
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2013 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, no 1, 114-122 p.Article in journal (Refereed) Published
Abstract [en]

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, Ca2+, 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.

Place, publisher, year, edition, pages
Lippincott, Williams and Wilkins , 2013. Vol. 42, no 1, 114-122 p.
Keyword [en]
acute pancreatitis, peroxisome proliferator-activated receptor-alpha, Toll-like receptor
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-87959DOI: 10.1097/MPA.0b013e3182550cc4ISI: 000312560200019OAI: diva2:601034

Funding Agencies|National Natural Science Fund of China (NSFC key project)|308301003097292481170439|SRF for ROCS, SEM|20101174-4-2|research fund for the Doctoral Program of Higher Education, SEM|200806100058|

Available from: 2013-01-28 Created: 2013-01-28 Last updated: 2013-03-19

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Sun, Xiao-Feng
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OncologyFaculty of Health SciencesDepartment of Oncology UHL
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