title: Systemic differential gene regulation of the inter-α-trypsin inhibitor family in acute necrotizing pancreatitis in mice.
abstract: BACKGROUND
  Therapy for systemic complications in severe necrotizing pancreatitis remains symptomatic owing to the unavailability of more specific therapeutic targets. We investigated the differential gene expression in typically affected organs in a mouse model of severe necrotizing pancreatitis.
  
  
  METHODS
  Acute necrotizing pancreatitis was induced in mice by retrograde infusion of taurocholate into the common bile duct. Microarray hybridization was subsequently performed with mRNA isolated from the spleen, liver, intestine, and lungs. Additionally, quantitative real-time polymerase chain reaction was performed to confirm the microarray results.
  
  
  RESULTS
  Severe necrotizing pancreatitis induced widespread changes in gene expression, affecting 27.20% of the genes tested in the spleen and 29.07% in the liver. Fewer genes were differentially regulated in the intestine (10.28%) and the lungs (10.75%). Only 10 genes were found to be upregulated in all 4 organs using microarray analysis. This upregulation in all organs was confirmed by quantitative real-time polymerase chain reaction for only 3 molecules. These molecules were lipocalin 2, insulin-like growth factor binding protein 1, and CD14. Additionally we observed significantly aberrant gene regulation of inter-α-trypsin inhibitor family members in several organs.
  
  
  CONCLUSIONS
  Differential gene regulation in severe necrotizing pancreatitis is far more organ specific than anticipated, with only 3 molecules uniformly regulated systemically. The inter-α-trypsin inhibitor family of molecules appears to play a crucial biologic role in the systemic inflammatory response in acute pancreatitis. Finally, owing to its regulation and function, α1-microglobulin (or bikunin) may be a suitable predictive marker of the systemic inflammatory response syndrome in acute pancreatitis.
authors.affiliation: Department of General and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Seifert
authors.forename: Rolf-Pascal
authors.initials: RP
authors.lastname: Kurzinger
authors.forename: Ulrich T
authors.initials: UT
authors.lastname: Hopt
authors.forename: Uwe A
authors.initials: UA
authors.lastname: Wittel
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics; D000510:Alpha-Globulins / Q000235:genetics* / Q000502:physiology; D000818:Animals; D005786:Gene Expression Regulation; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics; D019283:Pancreatitis, Acute Necrotizing / Q000235:genetics*
chemical_list: D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D018970:Insulin-Like Growth Factor Binding Protein 1; D000071068:Lipocalin-2; D054834:Lipocalins; D018950:Lipopolysaccharide Receptors; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse; C011877:inter-alpha-inhibitor