Authors: | Gao, Yuying Song, Binbin Aoki, Shigeki Ito, Kousei |
Title: | Role of Kupffer cells in liver injury induced by CpG oligodeoxynucleotide and flucloxacillin in mice |
Language (ISO): | en |
Abstract: | CpG oligodeoxynucleotide (CpG-ODN) is a Toll-like receptor 9 (TLR9) agonist that can induce innate immune responses. In a previous study, flucloxacillin (FLUX; 100 mg/kg, gavage)-induced liver injury in mice was enhanced by co-administration of CpG-ODN (40 μg/mouse, intraperitoneally). In this study, the mechanism of CpG-ODN sensitization to FLUX-induced liver injury was further investigated in mice inhibited of Kupffer cells (KCs) function by gadolinium chloride (GdCl3; 10 mg/kg, intravenously). GdCl3-treated mice administrated with CpG-ODN and FLUX showed lower liver injury than wild-type (WT) mice treated with CpG-ODN and FLUX. Upregulation of Fas and FasL by CpG-ODN was also inhibited in GdCl3-treated mice and mitochondrial swelling in response to FLUX failed to occur regardless of pre-treatment with CpG-ODN. When FasL-mutant gld/gld mice were treated with CpG-ODN, mitochondrial swelling in response to FLUX was also inhibited. These results suggest that KCs play an essential role in liver injury induced by CpG-ODN and FLUX. CpG-ODN may activate KCs, resulting in induction of Fas/FasL-mediated apoptosis of hepatocytes. The Fas/FasL pathway may also be an upstream regulator of CpG-ODN- and FLUX-induced changes in mitochondrial permeability transition. These results enhance our understanding of the mechanism of the adjuvant effect of CpG-ODN in this mouse model of liver injury. |
Subject Headings: | Kupffer cells Toll-like receptor 9 Fas/Fas ligand Pro-inflammatory cytokines Mitochondrial permeability transition |
URI: | http://hdl.handle.net/2003/39839 http://dx.doi.org/10.17877/DE290R-21730 |
Issue Date: | 2020-03-13 |
Rights link: | https://creativecommons.org/licenses/by/4.0/ |
Provenance: | IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund |
Citation: | https://www.excli.de/index.php/excli/article/view/2023 |
Appears in Collections: | Original Articles 2020 |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Ito_13032020_proof.pdf | DNB | 994.77 kB | Adobe PDF | View/Open |
This item is protected by original copyright |
This item is licensed under a Creative Commons License