Original Articles
Copyright ©The Author(s) 2001. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 15, 2001; 7(2): 259-265
Published online Apr 15, 2001. doi: 10.3748/wjg.v7.i2.259
Stress kinase inhibition modulates acute experimental pancreatitis
F. Fleischer, R. Dabew, B. Gö ke, ACC Wagner
F. Fleischer, R. Dabew, B. Gö ke, ACC Wagner, Department of Gastroenterology, Inselspital, University of Bern, Switzerland
Author contributions: All authors contributed equally to the work.
Correspondence to: Andreas C.C. Wagner, Department of Gastroenterology, Inselspital, University of Bern, CH-3010 Bern, Switzerland. Awagner@dkf4.unibe.ch
Telephone: +41-(0)31-6328025 Fax: +41-(0)31-6329765
Received: February 6, 2001
Revised: February 22, 2001
Accepted: March 1, 2001
Published online: April 15, 2001

AIM: To examine the role of p38 during acute experimental cerulein pancreatitis.

METHODS: Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347) and/or a specific p38 inhbitor (SB203580) and pancreatic stress kinase activity was determined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology.

RESULTS: JNK inhibition with CEP1347 ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580 aggravated pancreatitis with higher trypsin levels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation. Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis.

CONCLUSION: Stress kinases modulate pancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis.

Keywords: pancreatitis, acute necrotizing/enzymology, cerulein/therapeutic use, Ca2+ calmodulin dependent protein kinase/metabolism, rats