dc.contributor.author
Kegel, Victoria
dc.contributor.author
Pfeiffer, Elisa
dc.contributor.author
Burkhardt, Britta
dc.contributor.author
Liu, Jia L.
dc.contributor.author
Zeilinger, Katrin
dc.contributor.author
Nüssler, Andreas K.
dc.contributor.author
Seehofer, Daniel
dc.contributor.author
Damm, Georg
dc.date.accessioned
2018-06-08T04:20:37Z
dc.date.available
2015-11-02T11:22:38.289Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/17090
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-21270
dc.description.abstract
Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction
leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue
stress/damage and therefore could be a tool for the estimation of consequent
effects associated with DILI. Aim of the present study was to establish a
human in vitro liver model for the investigation of immune-mediated signaling
in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver
specimens. The isolated KC yield was cells/g liver tissue with a purity of
>80%. KC activation was investigated by the measurement of reactive oxygen
intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC
activation levels showed broad donor variability. Additional activation of KC
using supernatants of hepatocytes treated with hepatotoxic drugs increased KC
activity and led to donor-dependent changes in the formation of ROI compared
to KC incubated with supernatants from untreated hepatocytes. Additionally, a
compound- and donor-dependent increase in proinflammatory cytokines or in
anti-inflammatory cytokines was detected. In conclusion, KC related immune
signaling in hepatotoxicity was successfully determined in a newly established
in vitro liver model. KC were able to detect hepatocyte stress/damage and to
transmit a donor- and compound-dependent immune response via cytokine
production.
en
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation
in a Human In Vitro Liver Model
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Mediators of Inflammation. - 2015 (2015), Artikel Nr. 640631
dcterms.bibliographicCitation.doi
10.1155/2015/640631
dcterms.bibliographicCitation.url
http://dx.doi.org/10.1155/2015/640631
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000023398
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000005615
dcterms.accessRights.openaire
open access