Protective role of hepatic non-parenchymal cells against drug-induced hepatocyte toxicity using perfluoropolyether-based microfluidic devices.

The role of hepatic non-parenchymal cells (NPCs) in drug-induced liver injury has been controversial. Utilizing our previously developed perfluoropolyether-based microfluidic devices-characterized by significantly reduced chemical absorption compared to conventional polydimethylsiloxane (PDMS)-we investigated the interactions between primary hepatocytes (PCs) and NPCs under physiologically relevant conditions. When exposed to coumarin or acetaminophen, PCs underwent severe cytotoxicity and showed glutathione (GSH) depletion. Notably, co-culture with NPCs restored drug-induced cytotoxicity and cellular GSH levels, accompanied by increased interleukin-6 (IL-6) secretion. Given previous reports linking IL-6 to cytochrome P450 expression modulation and glutathione synthesis, these findings suggest that IL-6 might be a critical mediator of protective effects exerted by NPCs. Using these microfluidic devices, we clearly demonstrated the protective roles of NPCs without interference from innate immune systems, offering novel insights into hepatocellular protection mechanisms.