Stress kinase inhibition modulates acute experimental pancreatitis.
OBJECTIVE
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.


CONCLUSIONS
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.
Fleischer
F
F
Department of Gastroenterology, Inselspital, University of Bern, CH-3010 Bern, Switzerland.
Dabew
R
R
Göke
B
B
Wagner
A C
AC
D000208:Acute Disease; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002108:Ceruletide; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023421:Models, Animal; D009336:Necrosis; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D014357:Trypsin / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007211:Indoles; D011725:Pyridines; C106592:3,9-bis((ethylthio)methyl)-K-252a; D002108:Ceruletide; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D014357:Trypsin; C093642:SB 203580