title: NF-kappaB activation in pancreas induces pancreatic and systemic inflammatory response.
abstract: OBJECTIVE
  The role of nuclear factor kappaB (NF-kappaB) activation in acute pancreatitis is uncertain. The transcription factor NF-kappaB is activated early in acute pancreatitis, and NF-kappaB is widely considered a key element in inflammatory responses based on its ability to regulate the expression of inflammatory mediators in vitro. However, its role in vivo in specific diseases remains unclear, and the current data on the role of NF-kappaB in acute pancreatitis is primarily correlative.
  
  
  METHODS
  In this study, NF-kappaB was directly activated within the pancreas using adenoviral-mediated transfer of an active subunit, RelA/p65 (Adp65), delivered by intraductal injection.
  
  
  RESULTS
  Administration of Adp65 led to the infection of a population of acinar cells within the pancreas, the activation of NF-kappaB, the expression of NF-kappaB target genes, and an inflammatory response. Administration of Adp65 increased the infiltration of neutrophils to the pancreas and lung and caused widespread damage to pancreatic acinar cells. In contrast, at the same titer, control adenovirus (AdGFP) had no effect on these parameters. The level of NF-kappaB activation and the severity of inflammation were reduced when an adenovirus bearing the inhibitory subunit IkappaB-alpha was coadministered with Adp65.
  
  
  CONCLUSIONS
  Thus, activation of NF-kappaB within the pancreas was sufficient for the initiation of an inflammatory response in this model. These results help define the specific role of NF-kappaB activation in acute pancreatitis.
authors.affiliation: Department of Physiology, University of Michigan, Ann Arbor, Michigan 48109-0622, USA.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Chen
authors.forename: Baoan
authors.initials: B
authors.lastname: Ji
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ernst
authors.forename: Diane
authors.initials: D
authors.lastname: Simeone
authors.forename: Craig D
authors.initials: CD
authors.lastname: Logsdon
mesh_terms: D000208:Acute Disease; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015870:Gene Expression / Q000502:physiology; D005822:Genetic Vectors; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D010179:Pancreas / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D051996:Transcription Factor RelA; D014362:Trypsinogen / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014362:Trypsinogen