15-Deoxy- γ 12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPAR γ and Reduction in NF- κ B Activity.

Kan Chen,Yingqun Zhou,Chengfen Wang,Yuanyuan Zheng,Jingjing Li,Huawei Zhang,Zhuoyi Fan,Chuanyong Guo,Fan Wang,Jie Lu,Rong Zhu,Ping Cheng,Jing Yang,Yan Zhang,Yujing Xia,Weiqi Dai,Junshan Wang,Miao Shen

doi:10.1155/2014/215631

Abstract

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.

Highlights

The incidence of hepatitis, or inflammation of the liver, has increased worldwide in the past few decades, threatening human health
Figure 4: 15d-PGJ2 upregulated PPARγ expression in liver cells (LO2) nuclei and suppressed the NF-κB activation in macrophages (RAW264.7). (a) The levels of NF-κB in the nuclei of LO2 cells were detected by western blot. (b) The western blot was used to analyze the levels of PPARγ in RAW264.7 cell nucleus. (c) The different expression of NF-κB in LO2 cellular localization were evaluated by immunofluorescence. (d) The expression of PPARγ in RAW264.7 cells was detected by immunofluorescence
Our results show that concanavalin A- (ConA-)induced liver injury was ameliorated in 15d-PGJ2pretreated mice, and this was accompanied by a reduction in the expression of proinflammatory cytokines and NF-κB activation

Summary

Objective

15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. We investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA-) induced autoimmune hepatitis in mice. The histological grade, proinflammatory cytokine levels, and NF-κB and PPARγ activity were determined 6, 12, and 24 h after the ConA injection. The NF-κB and PPARγ activity were determined 30 min after the ConA administration. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 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

Introduction

Materials and Methods

Results

Discussion