Abstract
Prior stress ameliorates caerulein-induced pancreatitis in rats. NF-kappaB is a proinflammatory transcription factor activated during caerulein pancreatitis. However, the effects of prior stress on pancreatic NF-kappaB activation are unknown. In the current study, the effect of prior water immersion stress on caerulein and tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappaB activation in the pancreas was evaluated. Water immersion of rats for up to 6 h prevents supramaximal caerulein-induced pancreatic IkappaB-alpha degradation and NF-kappaB activation in vivo. NF-kappaB activity is also inhibited in vitro in pancreatic acini prepared from water-immersed animals. TNF-alpha-induced NF-kappaB activation in pancreas or in pancreatic acini is unaffected by prior water immersion. Chelation of intracellular Ca(2+) by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate/acetoxymethyl ester has similar effects to water immersion in preventing caerulein but not TNF-alpha-induced NF-kappaB activation in pancreas. Both the spike response and the sustained rise in [Ca(2+)](i) in response to supramaximal caerulein stimulation are reduced markedly in acini prepared from water-immersed animals as compared with normal animals. Our findings indicate that, in addition to Ca(2+)-dependent mechanisms, Ca(2+)-independent signaling events also may lead to NF-kappaB activation in pancreatic acinar cells. Water immersion stress prevents supramaximal caerulein-induced NF-kappaB activation in pancreas in vivo and in vitro by affecting intracellular Ca(2+) homeostasis.
Highlights
Doses of caerulein, the decapeptide analog of cholecystokinin, in excess of those that elicit a maximal rate of digestive enzyme secretion from the rat pancreas, elicit a reversible form of acute interstitial pancreatitis
We have shown recently that prior water immersion stress, under conditions that result in expression of heat shock protein 60 (HSP60),1 prevents caerulein-induced in vivo activation of trypsinogen in acinar cells and protects against this form of secretagogue-induced pancreatitis [3]
Pancreatic acinar cell Nuclear factor-B (NF-B) activation has been reported to occur during the very early stages of caerulein-induced pancreatitis [6, 7] and evidence has been presented that suggests that prevention of caerulein-induced NF-B activation in the pancreas can ameliorate the severity of caerulein-induced pancreatitis [6]
Summary
The decapeptide analog of cholecystokinin, in excess of those that elicit a maximal rate of digestive enzyme secretion from the rat pancreas, elicit a reversible form of acute interstitial pancreatitis This model of pancreatitis, referred to as secretagogue-induced pancreatitis, is associated with and possibly brought about by intra-acinar cell activation of digestive enzyme zymogens including trypsinogen [1]. We have shown recently that prior water immersion stress, under conditions that result in expression of heat shock protein 60 (HSP60), prevents caerulein-induced in vivo activation of trypsinogen in acinar cells and protects against this form of secretagogue-induced pancreatitis [3]. Supramaximal stimulation of acini in vitro with caerulein causes activation of NF-B by a mechanism that has been shown to involve a rise in cytoplasmic free calcium levels ([Ca2ϩ]i) and activation of protein kinase C (8 –9)
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