title: Altered biliary epithelial cell and monocyte responses to lipopolysaccharide as a TLR ligand in patients with primary biliary cirrhosis.
abstract: OBJECTIVE
  Lipopolysaccharide (LPS) is suspected to trigger primary biliary cirrhosis (PBC) in susceptible individuals, yet the precise mechanism of its effect in PBC remains largely unknown. The aim of this study was to investigate altered responses to LPS ligand for Toll-like receptors (TLRs) in pathogenesis of PBC in vivo and in vitro.
  
  
  METHODS
  In vivo, we investigated levels of LPS and pro-inflammatory cytokines in sera and expression of LPS receptors in liver tissues from 162 patients with PBC, 325 patients with other liver diseases and 80 healthy controls. In vitro, altered responses to LPS on monocytes and cultured human biliary epithelial cells (BECs) from patients with PBC were determined.
  
  
  RESULTS
  Significantly higher levels of LPS in patients with PBC were detected, compared with patients with other liver diseases and healthy controls. Immunohistochemically, expression of TLR4, CD14, CD68 and NF-κB was significantly enhanced in liver tissues from patients with PBC. Before LPS stimulation, we found significantly higher serum levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8 in patients with PBC than those in healthy controls. After LPS stimulation, TLR4 expression and pro-inflammatory cytokine production in CD14-positive monocytes and cultured BEC from patients with PBC increased significantly.
  
  
  CONCLUSIONS
  These results indicated that patients with PBC were prone to exhibit higher serum LPS level, hypersensitivity of monocytes and BEC to LPS, and enhanced production of pro-inflammatory cytokines. LPS altered expression of TLR4, CD14 and NF-κB on monocytes and BEC, which may be implicated in the pathogenesis and progression of PBC.
authors.affiliation: Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China. jmzhao302@163.com
authors.forename: Jingmin
authors.initials: J
authors.lastname: Zhao
authors.forename: Suxian
authors.initials: S
authors.lastname: Zhao
authors.forename: Guangde
authors.initials: G
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Guo
authors.forename: Panyong
authors.initials: P
authors.lastname: Mao
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Zhou
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Yuemin
authors.initials: Y
authors.lastname: Nan
authors.forename: Dongping
authors.initials: D
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D019694:Hepatitis B, Chronic / Q000378:metabolism; D019693:Hepatitis, Autoimmune / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary / Q000209:etiology* / Q000276:immunology / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood; D000097802:CD83 Antigen; D000097382:CD68 Molecule
chemical_list: D000469:Alkaline Phosphatase; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001663:Bilirubin; D007136:Immunoglobulins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D005723:gamma-Glutamyltransferase; D000097802:CD83 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule