Journal article
Stress kinase inhibition modulates acute experimental pancreatitis.
- Fleischer F Department of Gastroenterology, Inselspital, University of Bern, CH-3010 Bern, Switzerland.
- Dabew R
- Göke B
- Wagner AC
- 2002-01-31
Published in:
- World journal of gastroenterology. - 2001
Acute Disease
Animals
Carbazoles
Ceruletide
Enzyme Inhibitors
Imidazoles
Indoles
Mitogen-Activated Protein Kinases
Models, Animal
Necrosis
Pancreatitis
Pyridines
Rats
Trypsin
p38 Mitogen-Activated Protein Kinases
English
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 inhibitor (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.
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 inhibitor (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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.3748/wjg.v7.i2.259
- PMID 11819771
- Persistent URL
- https://sonar.ch/global/documents/891
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