Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Pro-inflammatory cytokines enhance dilatation of bile canaliculi caused by cholestatic antibiotics

Abstract : 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.
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [38 références]  Voir  Masquer  Télécharger
Déposant : Laurent Jonchère <>
Soumis le : mardi 2 juillet 2019 - 14:35:15
Dernière modification le : mercredi 17 février 2021 - 17:10:07


Fichiers produits par l'(les) auteur(s)



Ahmad Sharanek, Audrey Burban, Nadia Ciriaci, André Guillouzo. Pro-inflammatory cytokines enhance dilatation of bile canaliculi caused by cholestatic antibiotics. Toxicology in Vitro, Elsevier, 2019, 58, pp.51-59. ⟨10.1016/j.tiv.2019.03.015⟩. ⟨hal-02087902⟩



Consultations de la notice


Téléchargements de fichiers