NF-kappaB activation in pancreas induces pancreatic and systemic inflammatory response.
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.
Chen
Xueqing
X
Department of Physiology, University of Michigan, Ann Arbor, Michigan 48109-0622, USA.
Ji
Baoan
B
Han
Bing
B
Ernst
Stephen A
SA
Simeone
Diane
D
Logsdon
Craig D
CD
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
D016328:NF-kappa B; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014362:Trypsinogen