title: Endotoxin and CD14 in the progression of biliary atresia.
abstract: BACKGROUND
  Biliary atresia (BA) is a typical cholestatic neonatal disease, characterized by obliteration of intra- and/or extra-hepatic bile ducts. However, the mechanisms contributing to the pathogenesis of BA remain uncertain. Because of decreased bile flow, infectious complications and damaging endotoxemia occur frequently in patients with BA. The aim of this study was to investigate endotoxin levels in patients with BA and the relation of these levels with the expression of the endotoxin receptor, CD14.
  
  
  METHODS
  The plasma levels of endotoxin and soluble CD14 were measured with a pyrochrome Limulus amebocyte lysate assay and enzyme-linked immunosorbent assay in patients with early-stage BA when they received the Kasai procedure (KP), in patients who were jaundice-free post-KP and followed-up at the outpatient department, in patients with late-stage BA when they received liver transplantation, and in patients with choledochal cysts. The correlation of CD14 expression with endotoxin levels in rats following common bile duct ligation was investigated.
  
  
  RESULTS
  The results demonstrated a significantly higher hepatic CD14 mRNA and soluble CD14 plasma levels in patients with early-stage BA relative to those with late-stage BA. However, plasma endotoxin levels were significantly higher in both the early and late stages of BA relative to controls. In rat model, the results demonstrated that both endotoxin and CD14 levels were significantly increased in liver tissues of rats following bile duct ligation.
  
  
  CONCLUSIONS
  The significant increase in plasma endotoxin and soluble CD14 levels during BA implies a possible involvement of endotoxin stimulated CD14 production by hepatocytes in the early stage of BA for removal of endotoxin; whereas, endotoxin signaling likely induced liver injury and impaired soluble CD14 synthesis in the late stages of BA.
authors.affiliation: Institute of Basic Medical Sciences, National Chang Kung University, Tainan, Taiwan.
authors.forename: Ming-Huei
authors.initials: MH
authors.lastname: Chou
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
authors.forename: Hock-Liew
authors.initials: HL
authors.lastname: Eng
authors.forename: Ching-Mei
authors.initials: CM
authors.lastname: Chen
authors.forename: Chiou-Huey
authors.initials: CH
authors.lastname: Wang
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
authors.forename: Tsun-Mei
authors.initials: TM
authors.lastname: Lin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001656:Biliary Atresia / Q000097:blood* / Q000201:enzymology / Q000473:pathology; D001663:Bilirubin / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004731:Endotoxins / Q000097:blood* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D008050:Lipid A / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood* / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D004731:Endotoxins; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D000410:Alanine Transaminase; D001663:Bilirubin