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.

Original languageEnglish
Pages (from-to)556-563
Number of pages8
JournalDigestive Diseases and Sciences
Volume53
Issue number2
DOIs
Publication statusPublished - Feb 2008

Fingerprint

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

Keywords

  • α-Melanocyte-stimulating hormone
  • Bile duct ligation
  • Cholestasis
  • Gene transfer
  • Inflammation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

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.

In: Digestive Diseases and Sciences, Vol. 53, No. 2, 02.2008, p. 556-563.

Research output: Contribution to journalArticle

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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.",
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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

PY - 2008/2

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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.

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