title: Expression of toll-like receptors 1-5 but not TLR 6-10 is elevated in livers of patients with non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  Animal models of non-alcoholic fatty liver disease (NAFLD) suggest that an increased translocation of bacterial endotoxins, leading to an activation of toll-like receptor-dependent signalling cascades (TLRs) and increased formation of reactive oxygen species, may add to development of insulin resistance and induction of plasminogen activator inhibitor-1 (PAI-1) in the liver. If similar mechanisms are also involved in the development of NAFLD in humans remains to be determined.
  
  
  METHODS
  Toll-like receptor (1-10), myeloid differentiation primary response gene (MyD88), interferon regulatory transcription factor 3 (IRF-3) and insulin receptor substrate 1 (IRS-1) mRNA expression was determined in liver samples of 11 patients with NAFLD and 11 controls. Hepatic PA1-1 and 4-hydroxynonenal protein adducts (4-HNE) levels were determined by immunohistochemistry.
  
  
  RESULTS
  Hepatic TLR 1-5 mRNAs expression was significantly higher in livers of NAFLD patients than in controls, whereas expression of TLR 6-10 mRNAs did not differ between groups. Expression of MyD88 but not IRF-3 was also significantly higher in livers of NAFLD patients than in controls. These alterations were associated with significantly higher levels of 4-HNE and PAI-1 protein levels in livers of NAFLD patients than in controls, whereas IRS-1 mRNA expression was ~80% lower in livers of NAFLD patients than in controls.
  
  
  CONCLUSIONS
  Taken together, these findings add further weight to the hypothesis that alterations at the level of intestine and intestinal barrier function may be critical in the development of NAFLD in humans.
authors.affiliation: Department of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Giridhar
authors.initials: G
authors.lastname: Kanuri
authors.forename: Ruth
authors.initials: R
authors.lastname: Ladurner
authors.forename: Julia
authors.initials: J
authors.lastname: Skibovskaya
authors.forename: Astrid
authors.initials: A
authors.lastname: Spruss
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Bischoff
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D017931:DNA Primers; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D050838:Interferon Regulatory Factor-3; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D051193:Toll-Like Receptors; C027576:4-hydroxy-2-nonenal
keywords: inflammation; insulin resistance; lipid peroxidation; toll-like receptors