Water immersion stress prevents caerulein-induced pancreatic acinar cell nf-kappa b activation by attenuating caerulein-induced intracellular Ca2+ changes.
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.
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
A J
AJ
Hietaranta
V P
VP
Singh
L
L
Bhagat
G J
GJ
van Acker
A M
AM
Song
A
A
Mykoniatis
M L
ML
Steer
A K
AK
Saluja
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002108:Ceruletide / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D020672:I-kappa B Proteins; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013312:Stress, Physiological; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014867:Water / Q000378:metabolism*
D002614:Chelating Agents; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D000072000:NF-KappaB Inhibitor alpha; D002108:Ceruletide; D002118:Calcium