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

Chen,Yun-Xin; Huang,Yue-Hong; Zheng,Wei-Da; Chen,Zhi-Xin; Zhang,Li-Juan; Wang,Xiao-Zhong

doi:10.3892/mmr.2012.1228

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

Authors:
- Yun-Xin Chen
- Yue-Hong Huang
- Wei-Da Zheng
- Zhi-Xin Chen
- Li-Juan Zhang
- Xiao-Zhong Wang
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Affiliations: Department of Gastroenterology, Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian, P.R. China
Published online on: December 11, 2012 https://doi.org/10.3892/mmr.2012.1228
Pages: 371-378

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Abstract

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.

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