Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis in vivo.

Activation of the inhibitor of NF-kappaB kinase/NF-kappaB (IKK/NF-kappaB) system and expression of proinflammatory mediators are major events in acute pancreatitis. However, the in vivo consequences of IKK activation on the onset and progression of acute pancreatitis remain unclear. Therefore, we modulated IKK activity conditionally in pancreatic acinar cells.

Cellular immune reaction in the pancreas is induced by constitutively active IkappaB kinase-2.

Background: Activation of the nuclear factor kappaB (NF-kappaB) system is a major event in acute and chronic inflammatory processes. NF-kappaB cascades are comprised of IkappaB kinases, IkappaBs and NF-kappaB dimers. Little is known of the individual roles of these proteins in organ specific inflammation.

Acute pancreatitis.

Acute pancreatitis is associated with significant morbidity and a mortality rate of approximately 8%. In severe pancreatitis, necrosis at the site of inflammation and remote organ failure develop in the course of disease. Pancreatic injury is initiated by molecular events in acinar cells.

Mitogenic and antiapoptotic role of constitutive NF-kappaB/Rel activity in pancreatic cancer.

The transcription factor NF-kappaB/Rel was found to be constitutively activated in human pancreatic cancer. RelA is present in the nucleus in primary human pancreatic cancer samples as well as in pancreatic cancer cell lines. NF-kappaB/Rel-binding activity consists of NF-kappaB1(p50) and RelA(p65).

Induction of IkappaB-kinase by cholecystokinin is mediated by trypsinogen activation in rat pancreatic lobules.

Background And Aims: Supramaximal concentrations of cholecystokinin (CCK) or cerulein induce the intracellular activation of trypsinogen and the transcription factor NF-kappaB, a key regulator of inflammatory gene expression. Both events occur early in the development of an acute pancreatitis. The aim of this study was to examine the relationship between intracellular trypsinogen and NF-kappaB activation.

Stat3 and NF-kappaB activation prevents apoptosis in pancreatic carcinogenesis.

Background & Aims: Human pancreatic adenocarcinoma has an overall poor prognosis. Therapeutic efforts are often ineffective because of late diagnosis and a high degree of chemoresistance. Overexpression of transforming growth factor alpha in the pancreas of transgenic mice causes the formation of premalignant ductal lesions and the development of invasive ductal adenocarcinoma.

Different modes of NF-kappaB/Rel activation in pancreatic lobules.

The eukaryotic transcription factor nuclear factor-kappaB (NF-kappaB)/Rel is activated by a large variety of stimuli. It has been demonstrated that NF-kappaB/Rel is induced during the course of cerulein pancreatitis. Here, we show that NF-kappaB/Rel is differentially activated in pancreatic lobules.

Transgenic overexpression of amphiregulin induces a mitogenic response selectively in pancreatic duct cells.

Background & Aims: The epidermal growth factor (EGF) receptor family and the corresponding ligands are frequently overexpressed in pancreatic cancer. To compare the biological effects of transforming growth factor (TGF)-alpha and amphiregulin (AR) on growth and differentiation of the exocrine pancreas, we have generated transgenic mice overexpressing AR under control of the elastase promoter.

Methods: Two independently generated transgenic mouse lines overexpress 50-, 43-, 28-, 26-, and 16-kilodalton AR forms in the pancreas.