Pro-inflammatory cytokines enhance dilatation of bile canaliculi caused by cholestatic antibiotics
In: ISSN: 0887-2333, 2019
Online
academicJournal
Zugriff:
International audience ; Many drugs can induce liver injury, characterized by hepatocellular, cholestatic or mixed hepatocellular-cholestatic lesions. While an inflammatory stress is known to aggravate hepatocellular injury caused by some drugs much less evidence exists for cholestatic features. In this study, the influence of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α), either individually or combined, on cytotoxic and cholestatic properties of antibiotics was evaluated using differentiated HepaRG cells. Six antibiotics of various chemical structures and known to cause cholestasis and/or hepatocellular injury in clinic were investigated. Caspase-3 activity was increased with all these tested hepatotoxic drugs and except with erythromycin, was further augmented in presence of cytokines mainly when these were co-added as a mixture. TNF-α and IL-1β aggravated cytotoxicity of TVX more than IL-6. Bile canaliculi (BC) dilatation induced by cholestatic drugs was increased by co-treatment with IL-6 and IL-1β but not with TNF-α. Reduced accumulation of carboxy-dichlorofluorescein, a substrate of the multi-drug resistance-associated protein 2, in antibiotic-induced dilatated BC, was further extended in presence of individual or mixed cytokines. In conclusion, our data demonstrate that pro-inflammatory cytokines either individually or in mixture, can modulate cholestatic and/or cytotoxic responses to antibiotics and that the extent of these effects is dependent on the cytokine and the cholestatic antibiotic.
Titel: |
Pro-inflammatory cytokines enhance dilatation of bile canaliculi caused by cholestatic antibiotics
|
---|---|
Autor/in / Beteiligte Person: | Sharanek, Ahmad ; Burban, Audrey ; Ciriaci, Nadia ; Guillouzo, André ; Nutrition, Métabolismes et Cancer (NuMeCan) ; Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; 115336, Innovative Medicines Initiative Joint Undertaking MIP-DIL ; FP7/20072013, European Union's Seventh Framework Programme ; companies, EFPIA ; MIP-DILI ProjectMIP-DILI Project ; National Council of Scientific and Technical Research ; National University of RosarioNational University of Rosario |
Link: | |
Zeitschrift: | ISSN: 0887-2333, 2019 |
Veröffentlichung: | HAL CCSD ; Elsevier, 2019 |
Medientyp: | academicJournal |
DOI: | 10.1016/j.tiv.2019.03.015 |
Schlagwort: |
|
Sonstiges: |
|