Interleukin-10 gene modification attenuates hepatocyte activation of rat hepatic stellate cells in vitro.

Activation of hepatic stellate cells (HSCs) plays a key role in the progression of liver fibrosis. Interleukin-10 (IL-10), a potential anti-fibrosis cytokine, has an unfavorable pharmacokinetic profile, which limits its clinical applications. A liver-targeting gene delivery system may maintain a longer-lasting concentration in hepatic tissue with fewer side‑effects in non-target tissues. In the present study, when delivered by asialoglycoprotein receptor-mediated liposomes, the IL-10 gene was highly expressed in BRL cells (a rat hepatocyte line) and attenuated the apoptosis of BRL cells induced by plasmid transfection. In a co-culture system, BRL cells demonstrated a marked ability to stimulate the proliferation of primary HSCs and their expression of α-SMA and procollagen type I. Following modification of the BRL cells with the IL-10 gene, this stimulation was attenuated and an accelerated apoptosis of the HSCs was induced. These results suggest that hepatocyte‑targeting gene delivery may be an ideal technique for the IL-10 gene therapy of liver fibrosis, which requires further confirmation by in vivo studies.