Loss of bile salt export pump aggravates lipopolysaccharide-induced liver injury in mice due to impaired hepatic endotoxin clearance

  1. Remetic, Jelena
  2. Ghallab, Ahmed ORCID logo
  3. Hobloss, Zaynab
  4. Brackhagen, Lisa
  5. Hassan, Reham ORCID logo
  6. Myllys, Maiju ORCID logo
  7. Radun, Richard
  8. Mlitz, Veronika
  9. Zhu, Ci
  10. Baumgartner, Maximilian
  11. Schrottmaier, Waltraud C.
  12. Mussbacher, Marion
  13. Timelthaler, Gerald
  14. Scharnagl, Hubert
  15. Stojakovic, Tatjana
  16. Assinger, Alice
  17. Fuchs, Claudia D.
  18. Hengstler, Jan ORCID logo
  19. Trauner, Michael ORCID logo

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Hepatology - 2021 - Remetic - Loss of bile salt export pump aggravates lipopolysaccharide‐induced liver injury in mice due.pdf 5,07MB
WeightNameValue
1000 Titel
  • Loss of bile salt export pump aggravates lipopolysaccharide-induced liver injury in mice due to impaired hepatic endotoxin clearance
1000 Autor/in
  1. Remetic, Jelena |
  2. Ghallab, Ahmed |
  3. Hobloss, Zaynab |
  4. Brackhagen, Lisa |
  5. Hassan, Reham |
  6. Myllys, Maiju |
  7. Radun, Richard |
  8. Mlitz, Veronika |
  9. Zhu, Ci |
  10. Baumgartner, Maximilian |
  11. Schrottmaier, Waltraud C. |
  12. Mussbacher, Marion |
  13. Timelthaler, Gerald |
  14. Scharnagl, Hubert |
  15. Stojakovic, Tatjana |
  16. Assinger, Alice |
  17. Fuchs, Claudia D. |
  18. Hengstler, Jan |
  19. Trauner, Michael |
1000 Erscheinungsjahr 2021
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-12-20
1000 Erschienen in
1000 Quellenangabe
  • 75(5):1095-1109
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1002/hep.32289 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306629/ |
1000 Ergänzendes Material
  • https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.32289#support-information-section |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • BACKGROUND AND AIMS: Lipopolysaccharide (LPS) clearance is delayed in cholestatic liver diseases. While compromised clearance by Kupffer cells (KCs) is involved, the role of LPS uptake into hepatocytes and canalicular excretion remains unclear. APPROACH AND RESULTS: Wild-type (WT) and bile salt export pump (Bsep) knockout (KO) mice were challenged i.p. with LPS. Liver injury was assessed by serum biochemistry, histology, molecular inflammation markers, and immune cell infiltration. LPS concentrations were determined in liver tissue and bile. Subcellular kinetics of fluorescently labeled LPS was visualized by intravital two-photon microscopy, and the findings in Bsep KO mice were compared to common bile duct–ligated (BDL) and multidrug resistance protein 2 (Mdr2) KO mice. Changes in gut microbiota composition were evaluated by 16S ribosomal RNA gene amplicon sequencing analysis. Bsep KO mice developed more pronounced LPS-induced liver injury and inflammatory signaling, with subsequently enhanced production of proinflammatory cytokines and aggravated hepatic immune cell infiltration. After LPS administration, its concentrations were higher in liver but lower in bile of Bsep KO compared to WT mice. Intravital imaging of LPS showed a delayed clearance from sinusoidal blood with a basolateral uptake block into hepatocytes and reduced canalicular secretion. Moreover, LPS uptake into KCs was reduced. Similar findings with respect to hepatic LPS clearance were obtained in BDL and Mdr2 KO mice. Pretreatment with the microtubule inhibitor colchicine inhibited biliary excretion of LPS in WT mice, indicating that LPS clearance is microtubule-dependent. Microbiota analysis showed no change of the gut microbiome between WT and Bsep KO mice at baseline but major changes upon LPS challenge in WT mice. CONCLUSIONS: Absence of Bsep and cholestasis in general impair LPS clearance by a basolateral uptake block into hepatocytes and consequently less secretion into canaliculi. Impaired LPS removal aggravates hepatic inflammation in cholestasis.
1000 Sacherschließung
lokal hepatocytes
lokal NF-kappaB
lokal Gut microbiota
lokal cholestasis
lokal biliary excretion
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/UmVtZXRpYywgSmVsZW5h|https://orcid.org/0000-0003-0695-3403|https://frl.publisso.de/adhoc/uri/SG9ibG9zcywgWmF5bmFi|https://frl.publisso.de/adhoc/uri/QnJhY2toYWdlbiwgTGlzYQ==|https://orcid.org/0000-0002-6569-7676|https://orcid.org/0000-0001-9117-4572|https://frl.publisso.de/adhoc/uri/UmFkdW4sIFJpY2hhcmQ=|https://frl.publisso.de/adhoc/uri/TWxpdHosIFZlcm9uaWth|https://frl.publisso.de/adhoc/uri/Wmh1LCBDaQ==|https://frl.publisso.de/adhoc/uri/QmF1bWdhcnRuZXIsIE1heGltaWxpYW4=|https://frl.publisso.de/adhoc/uri/U2Nocm90dG1haWVyLCBXYWx0cmF1ZCBDLg==|https://frl.publisso.de/adhoc/uri/TXVzc2JhY2hlciwgTWFyaW9u|https://frl.publisso.de/adhoc/uri/VGltZWx0aGFsZXIsIEdlcmFsZA==|https://frl.publisso.de/adhoc/uri/U2NoYXJuYWdsLCBIdWJlcnQ=|https://frl.publisso.de/adhoc/uri/U3RvamFrb3ZpYywgVGF0amFuYQ==|https://frl.publisso.de/adhoc/uri/QXNzaW5nZXIsIEFsaWNl|https://frl.publisso.de/adhoc/uri/RnVjaHMsIENsYXVkaWEgRC4=|https://orcid.org/0000-0002-1427-5246|https://orcid.org/0000-0002-1275-6425
1000 Label
1000 Förderer
  1. Austrian Science Foundation |
  2. Bundesministerium für Bildung und Forschung |
1000 Fördernummer
  1. I2755, DK-IAI W1212
  2. 031L0052; 031L0045
1000 Förderprogramm
  1. Doctoral program “Inflammation and Immunity
  2. Liver-LiSyM
1000 Dateien
  1. Loss of bile salt export pump aggravates lipopolysaccharide-induced liver injury in mice due to impaired hepatic endotoxin clearance
    Loss of bile salt export pump aggravates lipopolysaccharide-induced liver injury in mice due to impaired hepatic endotoxin clearance
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Austrian Science Foundation |
    1000 Förderprogramm Doctoral program “Inflammation and Immunity
    1000 Fördernummer I2755, DK-IAI W1212
  2. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm Liver-LiSyM
    1000 Fördernummer 031L0052; 031L0045
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6434775.rdf
1000 Erstellt am 2022-08-31T13:42:29.078+0200
1000 Erstellt von 254
1000 beschreibt frl:6434775
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Wed Sep 07 13:37:44 CEST 2022
1000 Objekt bearb. Wed Sep 07 13:37:30 CEST 2022
1000 Vgl. frl:6434775
1000 Oai Id
  1. oai:frl.publisso.de:frl:6434775 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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