IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis.
BACKGROUND:The role of inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH), a common cause of liver disease, is still poorly understood. This study aimed at assessing the involvement of a major inflammatory cytokine, IL-6, in NASH. MATERIALS AND METHODS:Steatohepatitis was induc...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-11-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2775411?pdf=render |
| _version_ | 1831670702620540928 |
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| author | Emmanuel Mas Marie Danjoux Virginie Garcia Stéphane Carpentier Bruno Ségui Thierry Levade |
| author_facet | Emmanuel Mas Marie Danjoux Virginie Garcia Stéphane Carpentier Bruno Ségui Thierry Levade |
| author_sort | Emmanuel Mas |
| collection | DOAJ |
| description | BACKGROUND:The role of inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH), a common cause of liver disease, is still poorly understood. This study aimed at assessing the involvement of a major inflammatory cytokine, IL-6, in NASH. MATERIALS AND METHODS:Steatohepatitis was induced by feeding wild-type or IL-6(-/-) mice for 5 weeks with a methionine and choline-deficient (MCD) diet. RESULTS:Whereas MCD diet-induced weight loss and decreases in serum glucose, cholesterol and triglyceride levels were similar in both genotypes, serum alanine aminotransferase was less elevated in IL-6(-/-) mice than in wild-type animals. Despite having a comparable liver steatosis score, IL-6-deficient mice exhibited less lobular inflammation than their wild-type littermates. Liver gene expression of TGF-beta and MCP-1 was also strongly attenuated in mutant mice; a more modest reduction was observed for PPAR-gamma and F4/80 transcripts as well as proteins. Chromatographic analysis of liver lipids demonstrated that MCD diet induced in normal and mutant mice a similar decrease in the ratio of phosphatidylcholine to phosphatidylethanolamine. However, the diet-induced increase in the levels of sphingomyelin and ceramide was less important in IL-6(-/-) mice. CONCLUSION:Altogether, these results indicate that IL-6 deficiency does not block the development of NASH; yet, IL-6 plays a critical role in the accompanying liver inflammation. |
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| format | Article |
| id | doaj.art-eb772f30040a4c73a86b19197d991b0e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T23:22:51Z |
| publishDate | 2009-11-01 |
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| series | PLoS ONE |
| spelling | doaj.art-eb772f30040a4c73a86b19197d991b0e2022-12-21T20:01:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-11-01411e792910.1371/journal.pone.0007929IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis.Emmanuel MasMarie DanjouxVirginie GarciaStéphane CarpentierBruno SéguiThierry LevadeBACKGROUND:The role of inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH), a common cause of liver disease, is still poorly understood. This study aimed at assessing the involvement of a major inflammatory cytokine, IL-6, in NASH. MATERIALS AND METHODS:Steatohepatitis was induced by feeding wild-type or IL-6(-/-) mice for 5 weeks with a methionine and choline-deficient (MCD) diet. RESULTS:Whereas MCD diet-induced weight loss and decreases in serum glucose, cholesterol and triglyceride levels were similar in both genotypes, serum alanine aminotransferase was less elevated in IL-6(-/-) mice than in wild-type animals. Despite having a comparable liver steatosis score, IL-6-deficient mice exhibited less lobular inflammation than their wild-type littermates. Liver gene expression of TGF-beta and MCP-1 was also strongly attenuated in mutant mice; a more modest reduction was observed for PPAR-gamma and F4/80 transcripts as well as proteins. Chromatographic analysis of liver lipids demonstrated that MCD diet induced in normal and mutant mice a similar decrease in the ratio of phosphatidylcholine to phosphatidylethanolamine. However, the diet-induced increase in the levels of sphingomyelin and ceramide was less important in IL-6(-/-) mice. CONCLUSION:Altogether, these results indicate that IL-6 deficiency does not block the development of NASH; yet, IL-6 plays a critical role in the accompanying liver inflammation.http://europepmc.org/articles/PMC2775411?pdf=render |
| spellingShingle | Emmanuel Mas Marie Danjoux Virginie Garcia Stéphane Carpentier Bruno Ségui Thierry Levade IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis. PLoS ONE |
| title | IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis. |
| title_full | IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis. |
| title_fullStr | IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis. |
| title_full_unstemmed | IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis. |
| title_short | IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis. |
| title_sort | il 6 deficiency attenuates murine diet induced non alcoholic steatohepatitis |
| url | http://europepmc.org/articles/PMC2775411?pdf=render |
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