title: Interferon gamma accelerates NF-kappaB activation of biliary epithelial cells induced by Toll-like receptor and ligand interaction.
abstract: BACKGROUND
  The Toll-like receptor (TLR) family recognises pathogen associated molecular patterns (PAMPs) and plays a pivotal role in the innate immune response. Biliary epithelial cells (BECs) lining the intrahepatic bile ducts are potentially exposed to bacterial components in bile, and murine BECs possess TLRs that recognise PAMPs, resulting in nuclear factor kappaB (NF-kappaB) activation.
  
  
  OBJECTIVE
  To examine the presence of TLRs in human BECs and the influence of cytokines and PAMPs on TLR expression and NF-kappaB activation.
  
  
  METHODS
  The expression of TLR2-5, MD-2, MyD88, and IRAK1 was examined in human liver tissue and cultured BECs by immunohistochemistry or reverse transcription polymerase chain reaction. The influence of PAMPs (peptidoglycan and lipopolysaccharide) in cultured cells preincubated with interferon gamma (IFNgamma) was evaluated by NF-kappaB activation.
  
  
  RESULTS
  TLR2-5, MyD88, and IRAK-1 proteins were detectable in BECs of the intrahepatic biliary tree in human liver tissue. TLR2-5, MD-2, MyD88, and IRAK-1 mRNA was demonstrated in human cultured BECs. The expression of these TLRs was upregulated by IFNgamma, and TLR2 was upregulated by tumour necrosis factor alpha. Interleukins 4 and 6 failed to induce TLR upregulation. Interestingly, preincubation with IFNgamma synergistically increased the upregulation of NF-kappaB induced by PAMPs in cultured BECs.
  
  
  CONCLUSIONS
  These results suggest that the TLR family is present in human biliary cells and participates in the innate immunity of the intrahepatic biliary tree. Disordered regulation of TLRs after intracellular signalling by cytokines and PAMPs may be involved in immune mediated biliary diseases.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: K
authors.initials: K
authors.lastname: Isse
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000368:Aged; D001653:Bile Ducts, Intrahepatic / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D010457:Peptidoglycan / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D018121:Receptors, Cytokine / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D008024:Ligands; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; D010457:Peptidoglycan; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D051193:Toll-Like Receptors; D007371:Interferon-gamma