15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity

Objective. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA-) induced autoimmune hepa...

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Main Authors: Kan Chen, Jingjing Li, Junshan Wang, Yujing Xia, Weiqi Dai, Fan Wang, Miao Shen, Ping Cheng, Yan Zhang, Chengfen Wang, Jing Yang, Rong Zhu, Huawei Zhang, Yuanyuan Zheng, Jie Lu, Zhuoyi Fan, Yingqun Zhou, Chuanyong Guo
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2014/215631
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author Kan Chen
Jingjing Li
Junshan Wang
Yujing Xia
Weiqi Dai
Fan Wang
Miao Shen
Ping Cheng
Yan Zhang
Chengfen Wang
Jing Yang
Rong Zhu
Huawei Zhang
Yuanyuan Zheng
Jie Lu
Zhuoyi Fan
Yingqun Zhou
Chuanyong Guo
author_facet Kan Chen
Jingjing Li
Junshan Wang
Yujing Xia
Weiqi Dai
Fan Wang
Miao Shen
Ping Cheng
Yan Zhang
Chengfen Wang
Jing Yang
Rong Zhu
Huawei Zhang
Yuanyuan Zheng
Jie Lu
Zhuoyi Fan
Yingqun Zhou
Chuanyong Guo
author_sort Kan Chen
collection DOAJ
description Objective. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA-) induced autoimmune hepatitis in mice. Materials and Methods. In vivo, Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and 15d-PGJ2 (10 μg or 25 μg) was administered 1 h before the ConA injection. The histological grade, proinflammatory cytokine levels, and NF-κB and PPARγ activity were determined 6, 12, and 24 h after the ConA injection. In vitro, LO2 cells and RAW264.7 cells were pretreated with 15d-PGJ2 (2 μM) 1 h before the stimulation with ConA (30 μg/mL). The NF-κB and PPARγ activity were determined 30 min after the ConA administration. Results. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 15d-PGJ2 activated PPARγ, blocked the degradation of IκBα, and inhibited the translocation of NF-κB into the nucleus. Conclusion. These results indicate that 15d-PGJ2 protects against ConA-induced autoimmune hepatitis by reducing proinflammatory cytokines. This reduction in inflammation may correlate with the activation of PPARγ and the reduction in NF-κB activity.
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spelling doaj-art-711f696c6da6420db41d5930a5ee18e92025-02-03T06:12:18ZengWileyPPAR Research1687-47571687-47652014-01-01201410.1155/2014/21563121563115-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB ActivityKan Chen0Jingjing Li1Junshan Wang2Yujing Xia3Weiqi Dai4Fan Wang5Miao Shen6Ping Cheng7Yan Zhang8Chengfen Wang9Jing Yang10Rong Zhu11Huawei Zhang12Yuanyuan Zheng13Jie Lu14Zhuoyi Fan15Yingqun Zhou16Chuanyong Guo17Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaTongji University School of Medicine, Shanghai 200092, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaObjective. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA-) induced autoimmune hepatitis in mice. Materials and Methods. In vivo, Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and 15d-PGJ2 (10 μg or 25 μg) was administered 1 h before the ConA injection. The histological grade, proinflammatory cytokine levels, and NF-κB and PPARγ activity were determined 6, 12, and 24 h after the ConA injection. In vitro, LO2 cells and RAW264.7 cells were pretreated with 15d-PGJ2 (2 μM) 1 h before the stimulation with ConA (30 μg/mL). The NF-κB and PPARγ activity were determined 30 min after the ConA administration. Results. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 15d-PGJ2 activated PPARγ, blocked the degradation of IκBα, and inhibited the translocation of NF-κB into the nucleus. Conclusion. These results indicate that 15d-PGJ2 protects against ConA-induced autoimmune hepatitis by reducing proinflammatory cytokines. This reduction in inflammation may correlate with the activation of PPARγ and the reduction in NF-κB activity.http://dx.doi.org/10.1155/2014/215631
spellingShingle Kan Chen
Jingjing Li
Junshan Wang
Yujing Xia
Weiqi Dai
Fan Wang
Miao Shen
Ping Cheng
Yan Zhang
Chengfen Wang
Jing Yang
Rong Zhu
Huawei Zhang
Yuanyuan Zheng
Jie Lu
Zhuoyi Fan
Yingqun Zhou
Chuanyong Guo
15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity
PPAR Research
title 15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity
title_full 15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity
title_fullStr 15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity
title_full_unstemmed 15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity
title_short 15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity
title_sort 15 deoxy γ12 14 prostaglandin j2 reduces liver impairment in a model of cona induced acute hepatic inflammation by activation of pparγ and reduction in nf κb activity
url http://dx.doi.org/10.1155/2014/215631
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