机构:[1]Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, People’s Republic of China四川大学华西医院[2]Department of Gastroenterological Surgery, West China Hospital, Sichuan University, People’s Republic of China四川大学华西医院[3]Department of Oncology, Institute of Biomedicine and Surgery, University of Linko¨ping, Linko¨ping, Sweden.
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.
基金:
National Natural Science
Fund of China (NSFC key project Nos. 30830100, 30972924,
and 81170439); the project sponsored by SRF for ROCS, SEM
(No. 20101174-4-2); and the research fund for the Doctoral
Program of Higher Education, SEM (No. 200806100058).
语种:
外文
PubmedID:
中科院(CAS)分区:
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
推荐引用方式(GB/T 7714):
Ding Jun-Li,Zhou Zong-Guang,Zhou Xiang-Yu,et al.Attenuation of acute pancreatitis by peroxisome proliferator-activated receptor-α in rats: the effect on Toll-like receptor signaling pathways.[J].Pancreas.2013,42(1):114-22.doi:10.1097/MPA.0b013e3182550cc4.
APA:
Ding Jun-Li,Zhou Zong-Guang,Zhou Xiang-Yu,Zhou Bin,Wang Ling...&Li Yuan.(2013).Attenuation of acute pancreatitis by peroxisome proliferator-activated receptor-α in rats: the effect on Toll-like receptor signaling pathways..Pancreas,42,(1)
MLA:
Ding Jun-Li,et al."Attenuation of acute pancreatitis by peroxisome proliferator-activated receptor-α in rats: the effect on Toll-like receptor signaling pathways.".Pancreas 42..1(2013):114-22