title: NF-kappaB related abnormal hyper-expression of iNOS and NO correlates with the inflammation procedure in biliary atresia livers.
abstract: OBJECTIVE
  To study the expression of inducible nitric oxide synthase (iNOS) and its related regulators in biliary atresia (BA) livers and exlpore their relationships with the inflammation pathway in BA livers.
  
  
  METHODS
  The iNOS expression in livers of 38 cases of BA children, 15 cases of neonatal cholestasis (NC) children, and 18 cases of normal control were, respectively, examined and total nitric oxide (NO) metabolites concentration of all samples were calculated by a colorimetric method based on Griess reaction. The TdT-mediated dupt biotin nick end labeling (TUNEL) method was used to label the apoptotic bile duct epithelial cells and hepatocytes. The western blotting and immunohistochemistry methods to semi-quantitatively analyze the nuclear factor-kappaB (NF-kappaB) expression of each group were also used.
  
  
  RESULTS
  The iNOS expression intensity and total NO metabolites concentration of BA group (0.30 +/- 0.08, 90.40 +/- 12.46 micromol/L) were significantly higher than those of NC and normal control groups, P < 0.01. Correlation analysis showed a strong positive correlation between the serum AST level (152.76 +/- 29.59 U/L) and total NO metabolites concentration in BA group. Compared with the NC (32.47 +/- 5.55) and normal control (20.72 +/- 5.63) groups, a significantly higher apoptosis rate of intrahepatic bile duct epithelial cells was found in BA group (54.00 +/- 11.67) that tightly correlated with the iNOS intensity (r = 0.99, P < 0.01). The NF-kappaB intensity of BA group was also significantly higher than that of NC and normal control groups and had a strong positive correlation with the iNOS intensity (r = 0.97, P < 0.01).
  
  
  CONCLUSIONS
  The abnormal hyper-expression of iNOS may play an important role in mediating the inflammation procedure in BA livers. This change perhaps has some relationship with the high expression of NF-kappaB and NO. These regulators can up-regulate the apoptosis of bile duct epithelial cells in BA livers and cause the damage to liver tissues.
authors.affiliation: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China. surgeonhuang@126.com
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Si
authors.forename: Jie-Xiong
authors.initials: JX
authors.lastname: Feng
mesh_terms: D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D001656:Biliary Atresia / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D016022:Case-Control Studies; D003124:Colorimetry; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D007249:Inflammation / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases