Source:http://linkedlifedata.com/resource/pubmed/id/20368703
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2010-7-29
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pubmed:abstractText |
Inflammatory processes have an important role in the development of hepatic steatosis and progression to nonalcoholic steatohepatitis (NASH). Interleukin-6 (IL-6) is known to be a proinflammatory cytokine, but also promotes liver regeneration and protects the liver against various forms of damage. The role of IL-6/Glycoprotein 130 (GP130) in NASH remains unclear. In this study, we determined whether blocking IL-6/GP130 signaling prevents progression of steatohepatitis in a mouse NASH model. Six-week-old male C57/BL6 mice were fed either chow control or a methionine choline-deficient (MCD) diet for 8 weeks. Half of the MCD diet-fed mice were treated with 15 mg/kg rat anti-mouse IL-6 receptor antibody (MR16-1), intraperitoneally twice weekly, the remainder and chow-fed mice were injected with 15 mg/kg rat IgG as a control. Hepatic steatosis, injury, fibrosis, apoptosis, markers of lipid peroxidation/oxidant stress and IL-6-related gene expressions were evaluated. MR16-1 treatment decreased signal transducer and activator of transcription 3 activities and expression of suppressor of cytokine signaling 3 in MCD diet-treated mouse livers. Although this treatment enhanced intrahepatic lipid accumulation accompanied by increased sterol regulatory element-binding protein 1 and decreased peroxisome proliferator-activated receptor-alpha expression, elevated plasma alanine aminotransferase levels were improved with decreased plasma free fatty acid levels, lipid peroxidation/oxidant stress and hepatic apoptosis. Blocking IL-6/GP130 signaling by MR16-1 enhanced MCD diet-induced hepatic steatosis, but ameliorated liver injury. These findings suggest that hepatic IL-6 signaling has a protective role against the progression of hepatic steatosis but may enhance liver inflammation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alanine Transaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Choline,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Methionine,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1530-0307
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
90
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1169-78
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pubmed:meshHeading |
pubmed-meshheading:20368703-Alanine Transaminase,
pubmed-meshheading:20368703-Animals,
pubmed-meshheading:20368703-Choline,
pubmed-meshheading:20368703-Choline Deficiency,
pubmed-meshheading:20368703-Diet,
pubmed-meshheading:20368703-Fatty Liver,
pubmed-meshheading:20368703-Genes,
pubmed-meshheading:20368703-Interleukin-6,
pubmed-meshheading:20368703-Lipid Peroxidation,
pubmed-meshheading:20368703-Liver,
pubmed-meshheading:20368703-Male,
pubmed-meshheading:20368703-Methionine,
pubmed-meshheading:20368703-Mice,
pubmed-meshheading:20368703-Mice, Inbred C57BL,
pubmed-meshheading:20368703-PPAR alpha,
pubmed-meshheading:20368703-Receptors, Interleukin-6,
pubmed-meshheading:20368703-Signal Transduction,
pubmed-meshheading:20368703-Sterol Regulatory Element Binding Protein 1
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pubmed:year |
2010
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pubmed:articleTitle |
Blockade of interleukin-6 signaling enhances hepatic steatosis but improves liver injury in methionine choline-deficient diet-fed mice.
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pubmed:affiliation |
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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