Dataset Information

Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.

ABSTRACT:

Objective

Astaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation.

Materials and methods

Autoimmune hepatitis was induced in in Balb/C mice using ConA (25 mg/kg), and astaxanthin was orally administered daily at two doses (20 mg/kg and 40 mg/kg) for 14 days before ConA injection. Levels of serum liver enzymes and the histopathology of inflammatory cytokines and other maker proteins were determined at three time points (2, 8 and 24 h). Primary hepatocytes were pretreated with astaxanthin (80 ?M) in vitro 24 h before stimulation with TNF-? (10 ng/ml). The apoptosis rate and related protein expression were determined 24 h after the administration of TNF-?.

Results

Astaxanthin attenuated serum liver enzymes and pathological damage by reducing the release of inflammatory factors. It performed anti-apoptotic effects via the descending phosphorylation of Bcl-2 through the down-regulation of the JNK/p-JNK pathway.

Conclusion

This research firstly expounded that astaxanthin reduced immune liver injury in ConA-induced autoimmune hepatitis. The mode of action appears to be downregulation of JNK/p-JNK-mediated apoptosis and autophagy.

SUBMITTER: Li J

PROVIDER: S-EPMC4356569 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.

Li Jingjing J Xia Yujing Y Liu Tong T Wang Junshan J Dai Weiqi W Wang Fan F Zheng Yuanyuan Y Chen Kan K Li Sainan S Abudumijiti Huerxidan H Zhou Zheng Z Wang Jianrong J Lu Wenxia W Zhu Rong R Yang Jing J Zhang Huawei H Yin Qin Q Wang Chengfen C Zhou Yuqing Y Lu Jie J Zhou Yingqun Y Guo Chuanyong C

PloS one 20150311 3

<h4>Objective</h4>Astaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation.<h4>Materials and methods</h4>Autoimmune hepatitis was induced in in Balb/C mice us ...[more]

PMID: 25761053

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Project description:Autoimmune hepatitis (AIH) results from an autoimmune-mediated chronic inflammatory response against liver cells. Defective self-tolerance and dysfunctional dendritic cells (DCs) play a regulatory role in AIH. Itaconate has recently attracted attention in the field of immunometabolism because of its crucial role as an anti-inflammatory metabolite that negatively regulates the inflammatory response. However, the underlying mechanism of itaconate mediation of DCs in AIH remains unclear. In this study, we found that itaconate acts as an anti-inflammatory factor in the liver. Endogenous itaconate levels were significantly increased in mice with S100-induced AIH model and correlated with upregulation of the immune-responsive gene 1 expression. However, the anti-inflammatory response from endogenously itaconate may not represent the effects exogenously-produced itaconate. We investigated the anti-inflammatory response from exogenous itaconate in S100-induced AIH, and our results showed that itaconate treatment attenuated liver histopathological damage, hepatocyte apoptosis, aminotransferase elevation, and IL-6 production in the S100-induced AIH model. In addition, Itaconate decreased glycolysis to suppress the maturation of DCs in the liver and spleen of AIH models, thereby directly regulating differentiation of Th17 and Tregs in vivo. The percentage of Th17 cells among the CD4+ population were decreased and Tregs were increased (P < 0.05). Furthermore, Itaconate-induced bone marrow-derived monocytes suppressed CD4+cells proliferation. In vitro and in vivo, we found that itaconate suppressed autophagy via activating the PI3K/AKT/mTOR signalling pathway in bone marrow-derived DCs and liver tissues. We further investigated the function of Itaconate on DC-specific mTOR-deficient mice. mTOR-deficient DCs augmented inflammatory reactions in mTORDC-/- AIH mice and induced autophagy. MHY1485 (an agonist of mTOR) and itaconate significantly alleviated the inflammatory reaction and autophagy signalling. In conclusion, itaconate ameliorate liver inflammation in S100-induced AIH mice by regulating the PI3K/AKT/mTOR pathway to decrease DCs autophagy and maturation. These results provide insight useful for treating AIH.

Dataset Information

Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.

Objective

Materials and methods

Results

Conclusion

Publications

Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.

Similar Datasets

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