Common Bile Duct Ligation as Model for Secondary Biliary Cirrhosis

Campenhout, Sanne Van; Vlierberghe, Hans Van; Devisscher, Lindsey

doi:10.1007/978-1-4939-9420-5_15

Cited by 27 publications

(26 citation statements)

References 20 publications

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“…Macrophages are released and activated in the portal area of PBC patients to release a large amount of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, causing cascade inflammatory cytokine responses and severe liver injury (41). The western blot analysis concluded in this study that treating BDL mice with TGF-β1 reduced the expression of IL-1β, IL-6 and TNF-α, members of pro-inflammatory cytokines of which the latter two were linked to oxygen-radical-mediated liver injury and thus cholestatic hepatitis in recent studies (42). It suggests that they play critical roles in the formation of acute intrahepatic cholestasis (43).…”

Section: Discussionsupporting

confidence: 50%

Mechanism of TGF‑β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis

et al. 2020

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Effect of exogenous transforming growth factor-β1 (TGF-β1) on cholestatic mice by inhibiting Kupffer cell immune responses in liver was investigated. To induce cholestasis, BALB/c mice received a sham operation (Mock group), or underwent a bile duct ligation (BDL group) and then were subcutaneously injected with TGF-β1 at multiple sites (TGF group). Liver functions were evaluated according to the levels of alanine aminotransferase (ALT), aspartate aminotransferase AST and γ-glutamyltranspeptidase (γ-GT) in serum samples. Expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) was detected. Expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in Kupffer cells (KCs) of the liver was detected. The isolated KCs were divided into control group, LPS group, TGF group and Galunisertib group and western blot analysis was used to detect the expression of NF-κB, IL-6, IL-1β, TNF-α, iNOS and Arg-1. The percentage of CD40, CD86, CD204 and CD206 as macrophage cell surface antigens were measured by flow cytometry. The indexes of liver function and liver fibrosis of the mice in the TGF group were significantly lower than those in the BDL group (P<0.05). The levels of IL-1β, IL-6 and TNF-α in the liver were lower than those in the BDL group, while the level of IL-10 was significantly increased (P<0.05). M2-type transformation occurred in liver Kupffer cells of mice in the TGF group. In cell experiments, TGF treatment downregulated the expression of IL-1β, IL-6, TNF-α and NF-κB, increased the expression of IL-10, and induced M2-type transformation in macrophages (P<0.05). In conclusion, TGF-ß1 diminished the progression of cholestasis in mice by inhibiting the inflammatory response of KCs and regulating KC polarization.

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Section: Discussionsupporting

confidence: 50%

Mechanism of TGF‑β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis

et al. 2020

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“…In brief, animals were anaesthetized with isoflurane inhalation (Isoflo, Abbott, Belgium). Once fully sedated, a midline abdominal incision was made, after which the common bile duct could be isolated and ligated between 2 knots of non-resorbable suture (Silkan 5/0, Braun Aesculap, Germany), as previously described [1] . Control mice were sham operated, whereby the common bile duct was isolated, but not ligated.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…The animal protocols used in this study were evaluated and approved by the Ethical Committee of Experimental Animals at the Faculty of Medicine and Health Sciences, Ghent University, Belgium (ECD 15/36). Cholestasis was induced by performing bile duct ligation (BDL) surgery as previously described [1] . Control mice were sham operated, whereby the common bile duct was isolated, but not ligated.…”

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confidence: 99%

Dataset on transcriptomic profiling of cholestatic liver injury in an in vitro and in vivo animal model

Gijbels¹,

Devisscher

Vinken³

2020

Data in Brief

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The transcriptomic dataset (whole genome microarray Affymetrix Human U133 plus 2.0 and Affymetrix Mouse Genome 430 2.0) presented in this paper describes the differential gene expression profile of a human in vitro model of drug-induced cholestasis and a well-known mouse in vivo model of cholestasis. The in vitro model consists of human hepatoma HepaRG cells in monolayer configuration exposed to 3 different cholestatic drugs with or without bile acids. For in vivo modelling of cholestasis, mice were subjected to bile duct ligation surgery. Consecutive normalization, summarization and background adjustments have been made by means of Robust Multichip Average Express software.

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“…The animal protocols used in this study were evaluated and approved by the Ethical Committee of Experimental Animals at the Faculty of Medicine and Health Sciences, Ghent University, Belgium (ECD 15/36). Cholestatic liver injury was induced by performing BDL as previously described (Van Campenhout et al 2019). Briefly, mice were anaesthetized with isoflurane inhalation (Isoflo, Abbott, Belgium), a midline abdominal incision was made, and the common bile duct was isolated and ligated with two knots of non-resorbable suture (Silkan 5/0, Braun Aesculap, Germany).…”

Section: Animals and Treatmentmentioning

confidence: 99%

Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury

et al. 2020

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Adverse outcome pathways (AOPs) have been recently introduced as tools to map the mechanisms underlying toxic events relevant for chemical risk assessment. AOPs particularly depict the linkage between a molecular initiating event and an adverse outcome through a number of intermediate key events. An AOP has been previously introduced for cholestatic liver injury. The objective of this study was to test the robustness of this AOP for different types of cholestatic insult and the in vitro to in vivo extrapolation. For this purpose, in vitro samples from human hepatoma HepaRG cell cultures were exposed to cholestatic drugs (i.e. intrahepatic cholestasis), while in vivo samples were obtained from livers of cholestatic mice (i.e. extrahepatic cholestasis). The occurrence of cholestasis in vitro was confirmed through analysis of bile transporter functionality and bile acid analysis. Transcriptomic analysis revealed inflammation and oxidative stress as key events in both types of cholestatic liver injury. Major transcriptional differences between intrahepatic and extrahepatic cholestatic liver insults were observed at the level of cell death and metabolism. Novel key events identified by pathway analysis included endoplasmic reticulum stress in intrahepatic cholestasis, and autophagy and necroptosis in both intrahepatic as extrahepatic cholestasis. This study demonstrates that AOPs constitute dynamic tools that should be frequently updated with new input information.

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Common Bile Duct Ligation as Model for Secondary Biliary Cirrhosis

Cited by 27 publications

References 20 publications

Mechanism of TGF‑β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis

Mechanism of TGF‑β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis

Dataset on transcriptomic profiling of cholestatic liver injury in an in vitro and in vivo animal model

Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury

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