The Protective Effect of Intrasplenic Transplantation of Ad-IL-18BP/IL-4 Gene-Modified Fetal Hepatocytes on ConA-Induced Hepatitis in Mice

Shao, Xueting; Qian, Yun; Xu, Chi; Hong, Bo; Xu, Wanhong; Shen, Lei; Jin, Changzhong; Wu, Zhigang; Tong, Xiangmin; Yao, Hang‐Ping

doi:10.1371/journal.pone.0058836

Cited by 21 publications

(20 citation statements)

References 46 publications

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“…(n = 10 mice per group). ing the pathology of human autoimmune hepatitis (Shao et al, 2013). T cell-mediated hepatitis can be induced in mice by intravenous injection of Con A, which leads to polyclonal activation of T cells, resulting in clinical and histological patterns of acute hepatitis (Tiegs et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…As Con A-induced hepatitis is an experimental model mirroring the pathology of human autoimmune hepatitis (Shao et al, 2013), we tested whether DEX could function as a remedy. Mice injected with Con A developed acute hepatitis as indicated by elevated serum ALT and AST levels in the Con A group compared with NS group.…”

Section: Dexmedetomidine Decreased Levels Of Alt and Ast After Con A mentioning

confidence: 99%

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Dexmedetomidine premedication attenuates concanavalin A-induced hepatitis in mice

Wang

Zou

et al. 2014

J. Toxicol. Sci.

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-Activated T cells selectively induced by concanavalin A (Con A) in liver are subsequent efficient resolution of inflammation. Activated T cells infiltrating in liver combined with pro-inflammatory cytokines are the major causes in Con A-induced liver injury. In our study, C57/BL mice were injected with Con A combined with dexmedetomidine or not. ALT and AST in blood and histopathology of liver were measured. T cell infiltration in liver was examined by flow cytometry and pro-inflammatory cytokines including IL-6, IL-10, TNF-α, and IFN-γ in blood were measured by ELISA. The mRNA level of CXCL10 was detected by RT-PCR and the protein level of NF-κB was measured by Western-blot. We found that dexmedetomidine alleviated Con A-induced liver injury by down-regulating levels of ALT and AST in blood and the severity of histopathology, which reflect the severity of hepatitis induced by Con A. In addition, pro-inflammatory cytokines in blood were attenuated by dexmedetomidine. Dexmedetomidine restrained the phosphorylation of NF-κB IκBα and P-65 dramatically which may participate in the regulation of cytokines secretion. Moreover, CXCL10 mRNA attenuated by dexmedetomidine in liver may result in the lower level of CD4 + T cells infiltration in liver. These results suggested that dexmedetomidine might be a potential compound in treating T cell-mediated liver injury.

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Section: Discussionmentioning

confidence: 99%

Section: Dexmedetomidine Decreased Levels Of Alt and Ast After Con A mentioning

confidence: 99%

Dexmedetomidine premedication attenuates concanavalin A-induced hepatitis in mice

Wang

Zou

et al. 2014

J. Toxicol. Sci.

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“…In our study, IFN-γ, IL-6, and TNF-α in serum were separately measured by ELISA [15,18,19]. 16 h later, after the Con A intravenous infection, we found these pro-inflammatory cytokines were significantly increased in serum with the level of IFN-γ, IL-6, and TNF-α of the normal mice who were not injected Concanavalin A was in the zero level.…”

Section: Pro-inflammatory Cytokinesmentioning

confidence: 54%

“…So we show the change of T cells by calculating the percentage of CD4+ and CD8+ cells in the liver which used the flow cytometry ( Figures 3A and 3B) [14][15][16]. As expected, the percentage of CD4+ and CD8+ were different between the two groups after Concanavalin A injection.…”

Section: The Difference Of Cd4+ and Cd8+mentioning

confidence: 88%

The Comparison between HBV Transgenic Mice and Normal Mice after Being Injected Concanavalin A (Con A)

Cheng¹,

Liu²,

Mu³

et al. 2017

Pharm Anal Chem

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HBV transgenic mice are used as chronic hepatitis B models for research, but they cannot be infected by HBV to have the hepatitis B as the same as human. In the research, we explored the differences between HBV transgenic mice and normal mice who are injected the concanavalin, A which can injure the livers of the mice. We found some data to show the differences of them after the injection, such as weight, pictures of the liver tissue, alanine transaminase (ALT) and aspartate transaminase (AST) in the blood. The pro-inflammatory cytokines (IL-6, IFN-γ and TNF-α) and T cells (CD4+ cells and CD8+ cells) also showed the livers of HBV transgenic mice were more vulnerable to be hurt than normal mice.

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“…Recent studies demonstrated that activating phosphorylated Akt (p-Akt) significantly attenuated Con A-induced liver injury. 8 – 11 Apoptosis, known as type I programmed cell death, is also involved in Con A-induced hepatitis. 9 Members of the Bcl-2 family of proteins have an essential role in the apoptotic pathway: Bcl-2 and Bcl-xl as anti-apoptotic proteins, and Bax and Bad as pro-apoptotic proteins.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin reduces liver impairment in a model of concanavalin A-induced acute hepatitis in mice

Mao¹,

Wang²,

Yu³

et al. 2015

DDDT

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Background and aimsGhrelin is a 28-amino-acid gut hormone that was first discovered as a potent growth hormone secretagogue. Recently, it has been shown to exert a strong anti-inflammatory effect. The purpose of the study reported here was to explore the effect and mechanism of ghrelin on concanavalin (Con) A-induced acute hepatitis.MethodsBalb/C mice were divided into four groups: normal control (NC) (mice injected with vehicle [saline]); Con A (25 mg/kg); Con A + 10 μg/kg ghrelin; and Con A + 50 μg/kg ghrelin (1 hour before Con A injection). Pro-inflammatory cytokine levels were detected. Protein levels of phosphoinositide 3-kinase (PI3K); phosphorylated Akt (p-Akt); caspase 3, 8, and 9; and microtubule-associated protein 1 light chain 3 (LC3) were also detected. Perifosine (25 mM) (an Akt inhibitor) was used to investigate whether the protective effect of ghrelin was interrupted by an Akt inhibitor. Protein levels of p-AKT; Bcl-2; Bax; and caspase 3, 8, and 9 were also detected.ResultsAspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by ghrelin pretreatment in Con A-induced hepatitis. Inflammatory cytokines were significantly reduced by ghrelin pretreatment. Bcl-2; Bax; and caspase 3, 8, and 9 expression were also clearly affected by ghrelin pretreatment, compared with the Con A-treated group. However, the Akt kinase inhibitor reversed the decrease of Bax and caspase 3, 8, 9, and reduced the protein level of p-Akt and Bcl-2. Ghrelin activated the PI3K/Akt/Bcl-2 pathway and inhibited activation of autophagy.ConclusionOur results demonstrate that ghrelin attenuates Con A-induced acute immune hepatitis by activating the PI3K/Akt pathway and inhibiting the process of autophagy, which might be related to inhibition of inflammatory cytokine release, and prevention of hepatocyte apoptosis. These effects could be interrupted by an Akt kinase inhibitor.

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The Protective Effect of Intrasplenic Transplantation of Ad-IL-18BP/IL-4 Gene-Modified Fetal Hepatocytes on ConA-Induced Hepatitis in Mice

Cited by 21 publications

References 46 publications

Dexmedetomidine premedication attenuates concanavalin A-induced hepatitis in mice

Dexmedetomidine premedication attenuates concanavalin A-induced hepatitis in mice

The Comparison between HBV Transgenic Mice and Normal Mice after Being Injected Concanavalin A (Con A)

Ghrelin reduces liver impairment in a model of concanavalin A-induced acute hepatitis in mice

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