MiR-122 Release in Exosomes Precedes Overt Tolvaptan-Induced Necrosis in a Primary Human Hepatocyte Micropatterned Coculture Model.

ABSTRACT: Idiosyncratic drug-induced liver injury (IDILI) is thought to often result from an adaptive immune attack on the liver. However, it has been proposed that the cascade of events culminating in an adaptive immune response begins with drug-induced hepatocyte stress, release of exosomal danger signals, and innate immune activation, all of which may occur in the absence of significant hepatocelluar death. A micropatterned coculture model (HepatoPac) was used to explore the possibility that changes in exosome content precede overt necrosis in response to the IDILI drug tolvaptan. Hepatocytes from 3 human donors were exposed to a range of tolvaptan concentrations bracketing plasma Cmax or DMSO control continuously for 4, 24, or 72 h. Although alanine aminotransferase release was not significantly

SUBMITTER: Mosedale M 

PROVIDER: S-EPMC6257010 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature