Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI
Joint Authors
Nussler, Andreas K.
Kegel, Victoria
Pfeiffer, Elisa
Burkhardt, Britta
Liu, Jia L.
Zeilinger, Katrin
Seehofer, Daniel
Damm, Georg
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-09-28
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
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 1.2±0.9×106 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.
American Psychological Association (APA)
Kegel, Victoria& Pfeiffer, Elisa& Burkhardt, Britta& Liu, Jia L.& Zeilinger, Katrin& Nussler, Andreas K.…[et al.]. 2015. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI. Mediators of Inflammation،Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1072482
Modern Language Association (MLA)
Kegel, Victoria…[et al.]. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI. Mediators of Inflammation No. 2015 (2015), pp.1-14.
https://search.emarefa.net/detail/BIM-1072482
American Medical Association (AMA)
Kegel, Victoria& Pfeiffer, Elisa& Burkhardt, Britta& Liu, Jia L.& Zeilinger, Katrin& Nussler, Andreas K.…[et al.]. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI. Mediators of Inflammation. 2015. Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1072482
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1072482