α-Melanocyte-Stimulating Hormone Gene Transfer Attenuates Inflammation after Bile Duct Ligation in the Rat

Chien Che Wang, Jia Wei Lin, Liang Ming Lee, Chien Min Lin, Wen Ta Chiu, Hsin Te Pai, Kuo Sheng Hung

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Cholestasis occurs in a wide variety of human liver diseases, and hepatocellular injury is an invariant feature of cholestasis causing liver dysfunction and inflammation, promoting fibrogenesis, and ultimately leading to liver failure. α-Melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. The aim of this study was to investigate whether the gene transfer of α-MSH could attenuate hepatic inflammation after bile duct ligation in the rat. Studies were performed in bile duct-ligated (BDL) rats. Hydrodynamic-based gene transfection with α-MSH plasmid via rapid tail vein injection was performed 30 min after ligation of bile duct. The endpoints were studied as markers of inflammation 7 days after bile duct ligation. α-MSH expression in liver via a single administration of naked plasmid was demonstrated. Liver inflammation index, including neutrophil infiltration and serum alanine aminotransferase, were significantly reduced in α-MSH gene transfer rats. Markers for liver inflammation, including expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and inducible NO synthase (iNOS) mRNA, as assessed by real-time PCR, were also attenuated by α-MSH gene therapy. Expression of iNOS protein in liver diminished after α-MSH gene transfer. Consistent with these data, hepatic stellate cells (HSC) and Kupffer cells were markedly inhibited in α-MSH gene-treated rats. Our findings show that gene transfer of α-MSH could attenuate hepatic inflammation after bile duct ligation in the rat.
原文英語
頁(從 - 到)556-563
頁數8
期刊Digestive Diseases and Sciences
53
發行號2
DOIs
出版狀態已發佈 - 二月 2008

指紋

Melanocyte-Stimulating Hormones
Bile Ducts
Ligation
Inflammation
Genes
Liver
Cholestasis
Nitric Oxide Synthase
Liver Diseases
Plasmids
Hepatic Stellate Cells
Kupffer Cells
Neutrophil Infiltration
Liver Failure
Hydrodynamics
Alanine Transaminase
Interleukin-1
Genetic Therapy
Transfection
Tail

ASJC Scopus subject areas

  • Gastroenterology

引用此文

α-Melanocyte-Stimulating Hormone Gene Transfer Attenuates Inflammation after Bile Duct Ligation in the Rat. / Wang, Chien Che; Lin, Jia Wei; Lee, Liang Ming; Lin, Chien Min; Chiu, Wen Ta; Pai, Hsin Te; Hung, Kuo Sheng.

於: Digestive Diseases and Sciences, 卷 53, 編號 2, 02.2008, p. 556-563.

研究成果: 雜誌貢獻文章

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title = "α-Melanocyte-Stimulating Hormone Gene Transfer Attenuates Inflammation after Bile Duct Ligation in the Rat",
abstract = "Cholestasis occurs in a wide variety of human liver diseases, and hepatocellular injury is an invariant feature of cholestasis causing liver dysfunction and inflammation, promoting fibrogenesis, and ultimately leading to liver failure. α-Melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. The aim of this study was to investigate whether the gene transfer of α-MSH could attenuate hepatic inflammation after bile duct ligation in the rat. Studies were performed in bile duct-ligated (BDL) rats. Hydrodynamic-based gene transfection with α-MSH plasmid via rapid tail vein injection was performed 30 min after ligation of bile duct. The endpoints were studied as markers of inflammation 7 days after bile duct ligation. α-MSH expression in liver via a single administration of naked plasmid was demonstrated. Liver inflammation index, including neutrophil infiltration and serum alanine aminotransferase, were significantly reduced in α-MSH gene transfer rats. Markers for liver inflammation, including expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and inducible NO synthase (iNOS) mRNA, as assessed by real-time PCR, were also attenuated by α-MSH gene therapy. Expression of iNOS protein in liver diminished after α-MSH gene transfer. Consistent with these data, hepatic stellate cells (HSC) and Kupffer cells were markedly inhibited in α-MSH gene-treated rats. Our findings show that gene transfer of α-MSH could attenuate hepatic inflammation after bile duct ligation in the rat.",
keywords = "α-Melanocyte-stimulating hormone, Bile duct ligation, Cholestasis, Gene transfer, Inflammation",
author = "Wang, {Chien Che} and Lin, {Jia Wei} and Lee, {Liang Ming} and Lin, {Chien Min} and Chiu, {Wen Ta} and Pai, {Hsin Te} and Hung, {Kuo Sheng}",
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AU - Wang, Chien Che

AU - Lin, Jia Wei

AU - Lee, Liang Ming

AU - Lin, Chien Min

AU - Chiu, Wen Ta

AU - Pai, Hsin Te

AU - Hung, Kuo Sheng

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N2 - Cholestasis occurs in a wide variety of human liver diseases, and hepatocellular injury is an invariant feature of cholestasis causing liver dysfunction and inflammation, promoting fibrogenesis, and ultimately leading to liver failure. α-Melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. The aim of this study was to investigate whether the gene transfer of α-MSH could attenuate hepatic inflammation after bile duct ligation in the rat. Studies were performed in bile duct-ligated (BDL) rats. Hydrodynamic-based gene transfection with α-MSH plasmid via rapid tail vein injection was performed 30 min after ligation of bile duct. The endpoints were studied as markers of inflammation 7 days after bile duct ligation. α-MSH expression in liver via a single administration of naked plasmid was demonstrated. Liver inflammation index, including neutrophil infiltration and serum alanine aminotransferase, were significantly reduced in α-MSH gene transfer rats. Markers for liver inflammation, including expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and inducible NO synthase (iNOS) mRNA, as assessed by real-time PCR, were also attenuated by α-MSH gene therapy. Expression of iNOS protein in liver diminished after α-MSH gene transfer. Consistent with these data, hepatic stellate cells (HSC) and Kupffer cells were markedly inhibited in α-MSH gene-treated rats. Our findings show that gene transfer of α-MSH could attenuate hepatic inflammation after bile duct ligation in the rat.

AB - Cholestasis occurs in a wide variety of human liver diseases, and hepatocellular injury is an invariant feature of cholestasis causing liver dysfunction and inflammation, promoting fibrogenesis, and ultimately leading to liver failure. α-Melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. The aim of this study was to investigate whether the gene transfer of α-MSH could attenuate hepatic inflammation after bile duct ligation in the rat. Studies were performed in bile duct-ligated (BDL) rats. Hydrodynamic-based gene transfection with α-MSH plasmid via rapid tail vein injection was performed 30 min after ligation of bile duct. The endpoints were studied as markers of inflammation 7 days after bile duct ligation. α-MSH expression in liver via a single administration of naked plasmid was demonstrated. Liver inflammation index, including neutrophil infiltration and serum alanine aminotransferase, were significantly reduced in α-MSH gene transfer rats. Markers for liver inflammation, including expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and inducible NO synthase (iNOS) mRNA, as assessed by real-time PCR, were also attenuated by α-MSH gene therapy. Expression of iNOS protein in liver diminished after α-MSH gene transfer. Consistent with these data, hepatic stellate cells (HSC) and Kupffer cells were markedly inhibited in α-MSH gene-treated rats. Our findings show that gene transfer of α-MSH could attenuate hepatic inflammation after bile duct ligation in the rat.

KW - α-Melanocyte-stimulating hormone

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