title: 15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy.
abstract: OBJECTIVE
  In this study, we confirmed a protective effect of 15d-PGJ2 in concanavalin A (ConA)-induced fulminant hepatitis in mice and investigated the potential mechanism.
  
  
  METHODS
  Balb/C mice were injected with ConA (25mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5-10μg) was administered 30min after the ConA injection. The histological grade, pro-inflammatory cytokine and ROS levels, apoptosis and autophagy activity, the expression of HO-1, Nrf2, JNK and Bcl-2 activity were determined 2, 4, and 8h after the ConA injection.
  
  
  RESULTS
  Following ConA challenge, the expression of cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) was up-regulated. Treatment with 15d-PGJ2 reduced the pathological effects of ConA-induced fulminant hepatitis and significantly reduced the levels of TNF-α, IL-1β and ROS after injection. 15d-PGJ2 inhibited apoptosis and autophagic cell death, facilitated Nrf2 nuclear translocation, increased HO-1 expression and suppressed the JNK activation.
  
  
  CONCLUSIONS
  15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating the anti-oxidative stress factor HO-1 and reducing the production of cytokines and ROS, thereby inhibiting hepatic cell autophagy probably induced by ROS.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: cutking@126.com.
authors.forename: Kan
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: sealjj@126.com.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: Lrk678@126.com.
authors.forename: Sainan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: fengjiao080801@163.com.
authors.forename: Jiao
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: 1085336378@qq.com.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: klmn1334@sina.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The First Clinical Medical College of Nanjing Medical University, Nanjing 210029, China. Electronic address: Sylvia_rong@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The First Clinical Medical College of Nanjing Medical University, Nanjing 210029, China. Electronic address: 964949991@qq.com.
authors.forename: Shizan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The First affiliated hospital of Soochow University, Suzhou 215006, China. Electronic address: chengkeran@126.com.
authors.forename: Keran
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The First affiliated hospital of Soochow University, Suzhou 215006, China. Electronic address: zyq937065339@163.com.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The First affiliated hospital of Soochow University, Suzhou 215006, China. Electronic address: 1374437780@qq.com.
authors.forename: Shunfeng
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: fairywong04285@163.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: dai_yue@163.com.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: gagaxyj@126.com.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: kennisren@hotmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: yqzh02@163.com.
authors.forename: Yingqun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: guochuanyong@hotmail.com.
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Guo
mesh_terms: D000208:Acute Disease; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003208:Concanavalin A; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006505:Hepatitis / Q000188:drug therapy / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000293:injuries* / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C477819:15-deoxyprostaglandin J2; D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D051547:Heme Oxygenase-1; D048031:JNK Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2
keywords: 14-prostaglandin J2; 15-Deoxy-Δ12; Autophagy; Concanavalin A; HO-1; Nrf2