Stress kinase inhibition modulates acute experimental pancreatitis.

Abstract

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.

• Authors: F Fleischer, R Dabew, B Göke, A C Wagner
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 7 Issue 2 Pg. 259-65 (Apr 2001) ISSN: 1007-9327 [Print] United States
• PMID: 11819771 (Publication Type: Journal Article)

Chemical References

• Carbazoles
• Enzyme Inhibitors
• Imidazoles
• Indoles
• Pyridines
• 3,9-bis((ethylthio)methyl)-K-252a
• Ceruletide
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Trypsin
• SB 203580

Topics

• Acute Disease
• Animals
• Carbazoles (pharmacology)
• Ceruletide
• Enzyme Inhibitors (pharmacology)
• Imidazoles (pharmacology)
• Indoles (pharmacology)
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Models, Animal
• Necrosis
• Pancreatitis (chemically induced, metabolism, pathology)
• Pyridines (pharmacology)
• Rats
• Trypsin (metabolism)
• p38 Mitogen-Activated Protein Kinases