15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy
| Autor: | Keran Cheng, Kan Chen, Yingqun Zhou, Weiqi Dai, Yujing Xia, Fan Wang, Liwei Wu, Jie Lu, Chuanyong Guo, Jingjing Li, Rong Zhang, Tong Liu, Yuqing Zhou, Sainan Li, Shunfeng Zhou, Jiao Feng, Shizan Xu |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Programmed cell death NF-E2-Related Factor 2 medicine.medical_treatment Interleukin-1beta chemical and pharmacologic phenomena Pharmacology Hepatitis 03 medical and health sciences 0302 clinical medicine Phagosomes Autophagy Concanavalin A medicine Animals Fulminant hepatitis Cell Nucleus Acute liver injury Mice Inbred BALB C biology Prostaglandin D2 Tumor Necrosis Factor-alpha Chemistry JNK Mitogen-Activated Protein Kinases General Medicine Up-Regulation Enzyme Activation Disease Models Animal 030104 developmental biology Cytokine Liver Apoptosis 030220 oncology & carcinogenesis Acute Disease Immunology Hepatocytes biology.protein Hepatic stellate cell Reactive Oxygen Species Heme Oxygenase-1 |
| Zdroj: | Biomedicine & Pharmacotherapy. 80:183-192 |
| ISSN: | 0753-3322 |
| Popis: | 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. Materials and methods Balb/C mice were injected with ConA (25 mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5–10 μg) was administered 30 min 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 8 h 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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