Localized pancreatic NF-kappaB activation and inflammatory response in taurocholate-induced pancreatitis.
Transcription factor nuclear factor-kappaB (NF-kappaB) is activated in cerulein pancreatitis and mediates cytokine expression. The role of transcription factor activation in other models of pancreatitis has not been established. Here we report upregulation of NF-kappaB and inflammatory molecules, and their correlation with local pancreatic injury, in a model of severe pancreatitis. Rats received intraductal infusion of taurocholate or saline, and the pancreatic head and tail were analyzed separately. NF-kappaB and activator protein-1 (AP-1) activation were assessed by gel shift assay, and mRNA expression of interleukin-6, tumor necrosis factor-alpha, KC, monocyte chemoattractant protein-1, and inducible nitric oxide synthase was assessed by semiquantitative RT-PCR. Morphological damage and trypsin activation were much greater in the pancreatic head than tail, in parallel with a stronger activation of NF-kappaB and cytokine mRNA. Saline infusion mildly affected these parameters. AP-1 was strongly activated in both pancreatic segments after either taurocholate or saline infusion. NF-kappaB inhibition with N-acetylcysteine ameliorated the local inflammatory response. Correlation between localized NF-kappaB activation, cytokine upregulation, and tissue damage suggests a key role for NF-kappaB in the development of the inflammatory response of acute pancreatitis.
Vaquero
E
E
Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, California 90073, USA. evaquero@ucla.edu
Gukovsky
I
I
Zaninovic
V
V
Gukovskaya
A S
AS
Pandol
S J
SJ
D000681:Amylases / Q000097:blood; D000818:Animals; D002465:Cell Movement; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D008049:Lipase / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid; D014018:Tissue Distribution; D018808:Transcription Factor AP-1 / Q000502:physiology; D014357:Trypsin / Q000502:physiology
D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D013656:Taurocholic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008049:Lipase; D000681:Amylases; D014357:Trypsin