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

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机构: [1]Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, People’s Republic of China [2]Department of Gastroenterological Surgery, West China Hospital, Sichuan University, People’s Republic of China [3]Department of Oncology, Institute of Biomedicine and Surgery, University of Linko¨ping, Linko¨ping, Sweden.
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关键词: acute pancreatitis peroxisome proliferator-activated receptor-> Toll-like receptor

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

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出版当年[2013]版:
大类 | 3 区 医学
小类 | 3 区 胃肠肝病学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 胃肠肝病学
第一作者:
第一作者机构: [1]Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, People’s Republic of China
通讯作者:
通讯机构: [1]Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, People’s Republic of China [*1]Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Gaopeng St, No. 1 on Keyuan Rd 4, Chengdu 610041, Sichuan, People’s Republic of China
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