title: Interleukin-10 gene modification attenuates hepatocyte activation of rat hepatic stellate cells in vitro.
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.
authors.affiliation: Department of Gastroenterology, Union Hospital of Fujian Medical                     University, Fuzhou 350001, Fujian, P.R. China.
authors.forename: Yun-Xin
authors.initials: YX
authors.lastname: Chen
authors.forename: Yue-Hong
authors.initials: YH
authors.lastname: Huang
authors.forename: Wei-Da
authors.initials: WD
authors.lastname: Zheng
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Chen
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D000199:Actins; D024042:Collagen Type I; D008081:Liposomes; D016753:Interleukin-10