Attenuation of Acute Pancreatitis by Peroxisome Proliferator-Activated Receptor-α in Rats: The Effect on Toll-Like Receptor Signaling Pathways
2013 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, no 1, 114-122 p.Article in journal (Refereed) Published
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.
acute pancreatitis, peroxisome proliferator-activated receptor-alpha, Toll-like receptor
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-87959DOI: 10.1097/MPA.0b013e3182550cc4ISI: 000312560200019OAI: oai:DiVA.org:liu-87959DiVA: 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|2013-01-282013-01-282013-03-19