Interleukin-10 gene therapy reverses thioacetamide-induced liver fibrosis in mice.
Hepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. Interleukin-10 (IL-10) is a cytokine that downregulates the proinflammatory response and has a modulatory effect on hepatic fibrogenesis. The aim of this study was to investigate whether IL-10 gene therapy possesses anti-hepatic fibrogenesis in mice. Liver fibrosis was induced by long-term thioacetamide administration in mice. Human IL-10 expression plasmid was delivered via electroporation after liver fibrosis established. IL-10 gene therapy reversed hepatic fibrosis and prevented cell apoptosis in a thioacetamide-treated liver. RT-PCR revealed IL-10 gene therapy to reduce liver transforming growth factor-beta1, tumor necrosis factor-alpha, collagen alpha1, cell adhesion molecule, and tissue inhibitors of metalloproteinase mRNA upregulation. Following gene transfer, the activation of alpha-smooth muscle actin and cyclooxygenase-2 was significantly attenuated. In brief, IL-10 gene therapy might be an effective therapeutic reagent for liver fibrosis with potential future clinical applications.
Hung
Kung-Sheng
KS
Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Lee
Tsung-Hsing
TH
Chou
Wen-Ying
WY
Wu
Chia-Ling
CL
Cho
Chung-Lung
CL
Lu
Cheng-Nan
CN
Jawan
Bruno
B
Wang
Cheng-Haung
CH
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D017931:DNA Primers; D015316:Genetic Therapy; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016753:Interleukin-10 / Q000235:genetics*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000628:therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013853:Thioacetamide / Q000633:toxicity*
D017931:DNA Primers; D013853:Thioacetamide; D016753:Interleukin-10; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases