Role of Kupffer cells in liver injury induced by CpG oligodeoxynucleotide and flucloxacillin in mice
| dc.contributor.author | Gao, Yuying | |
| dc.contributor.author | Song, Binbin | |
| dc.contributor.author | Aoki, Shigeki | |
| dc.contributor.author | Ito, Kousei | |
| dc.date.accessioned | 2020-12-07T08:03:38Z | |
| dc.date.available | 2020-12-07T08:03:38Z | |
| dc.date.issued | 2020-03-13 | |
| dc.description.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. | en |
| dc.identifier.citation | https://www.excli.de/index.php/excli/article/view/2023 | de |
| dc.identifier.issn | 1611-2156 | |
| dc.identifier.uri | http://hdl.handle.net/2003/39839 | |
| dc.identifier.uri | http://dx.doi.org/10.17877/DE290R-21730 | |
| dc.language.iso | en | |
| dc.publisher | IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund | en |
| dc.relation.ispartofseries | EXCLI Journal;Vol. 19 2020 | |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
| dc.subject | Kupffer cells | en |
| dc.subject | Toll-like receptor 9 | en |
| dc.subject | Fas/Fas ligand | en |
| dc.subject | Pro-inflammatory cytokines | en |
| dc.subject | Mitochondrial permeability transition | en |
| dc.subject.ddc | 610 | |
| dc.title | Role of Kupffer cells in liver injury induced by CpG oligodeoxynucleotide and flucloxacillin in mice | en |
| dc.type | Text | |
| dc.type.publicationtype | article | |
| dcterms.accessRights | open access | |
| eldorado.dnb.zdberstkatid | 2132560-1 | |
| eldorado.secondarypublication | true |