15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy

Kan Chen; Jingjing Li; Sainan Li; Jiao Feng; Liwei Wu; Tong Liu; Rong Zhang; Shizan Xu; Keran Cheng; Yuqing Zhou; Shunfeng Zhou; Fan Wang; Weiqi Dai; Yujing Xia; Jie Lu; Yingqun Zhou; Chuanyong Guo

doi:10.1016/j.biopha.2016.03.012

15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy

Biomed Pharmacother. 2016 May:80:183-192. doi: 10.1016/j.biopha.2016.03.012. Epub 2016 Mar 26.

Authors

Kan Chen¹, Jingjing Li², Sainan Li³, Jiao Feng⁴, Liwei Wu⁵, Tong Liu⁶, Rong Zhang⁷, Shizan Xu⁸, Keran Cheng⁹, Yuqing Zhou¹⁰, Shunfeng Zhou¹¹, Fan Wang¹², Weiqi Dai¹³, Yujing Xia¹⁴, Jie Lu¹⁵, Yingqun Zhou¹⁶, Chuanyong Guo¹⁷

Affiliations

¹ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
² Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
³ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
⁴ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
⁵ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
⁶ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
⁷ 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: [email protected].
⁸ 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: [email protected].
⁹ 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: [email protected].
¹⁰ 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: [email protected].
¹¹ 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: [email protected].
¹² Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
¹³ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
¹⁴ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
¹⁵ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
¹⁶ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].
¹⁷ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: [email protected].

PMID: 27133055
DOI: 10.1016/j.biopha.2016.03.012

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.

Materials and 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.

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.

Keywords: 14-prostaglandin J2; 15-Deoxy-Δ12; Autophagy; Concanavalin A; HO-1; Nrf2.

MeSH terms

Acute Disease
Animals
Autophagy / drug effects*
Cell Nucleus / drug effects
Cell Nucleus / metabolism
Concanavalin A
Disease Models, Animal
Enzyme Activation / drug effects
Heme Oxygenase-1 / metabolism*
Hepatitis / drug therapy
Hepatitis / pathology
Hepatocytes / drug effects
Hepatocytes / pathology*
Hepatocytes / ultrastructure
Interleukin-1beta / metabolism
JNK Mitogen-Activated Protein Kinases / metabolism
Liver / drug effects
Liver / injuries*
Liver / pathology*
Liver / ultrastructure
Male
Mice, Inbred BALB C
NF-E2-Related Factor 2 / metabolism
Phagosomes / drug effects
Phagosomes / metabolism
Phagosomes / ultrastructure
Prostaglandin D2 / analogs & derivatives*
Prostaglandin D2 / pharmacology
Prostaglandin D2 / therapeutic use
Reactive Oxygen Species / metabolism
Tumor Necrosis Factor-alpha / metabolism
Up-Regulation / drug effects*

Substances

15-deoxyprostaglandin J2
Interleukin-1beta
NF-E2-Related Factor 2
Nfe2l2 protein, mouse
Reactive Oxygen Species
Tumor Necrosis Factor-alpha
Concanavalin A
Heme Oxygenase-1
JNK Mitogen-Activated Protein Kinases
Prostaglandin D2