Effects of mitogen-activated protein kinase signaling pathway inhibition on the development of cerulein-induced acute pancreatitis in mice.
OBJECTIVE
Extracellular signal-regulated kinase (ERK) influences a number of pathways in all cells. The ERK cascade has long been known to be central to the activation of cellular processes such as proliferation, differentiation, and oncogenic transformation. The mitogen-activated protein (MAP) serine/threonine family of protein kinases, of which ERK is a member, is evolutionarily conserved and is activated by a mechanism that includes protein kinase cascades. The aim of this study was to investigate the effects of PD98059 [2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one], a highly selective inhibitor of MAP/ERK kinase 1 (MEK1) activation, on the development of acute pancreatitis.


METHODS
Pancreatitis was induced by intraperitoneal injection of cerulein (hourly × 5, 50 μg/kg) and PD98059 (10 mg/kg, 10% dimethylsulfoxide, intraperitoneally) was administrated 1 and 3 hours after cerulein administration.


RESULTS
Cerulein injection resulted in acute necrotizing pancreatitis. On the contrary, pancreatitis histological features, amylase, lipase, pancreas edema, and immunohistochemical staining for leukocyte adhesion molecules, transforming growth factor β, and apoptosis-related proteins were found reduced in PD98059-treated mice.


CONCLUSIONS
We propose that this study could help to clarify the role of MAPK in the regulation of the inflammatory process as acute pancreatitis.
IRCCS Centro Neurolesi Bonino-Pulejo, School of Medicine, University of Messina, Messina, Italy.
Emanuela
E
Mazzon
Daniela
D
Impellizzeri
Rosanna
R
Di Paola
Irene
I
Paterniti
Emanuela
E
Esposito
Alessandro
A
Cappellani
Placido
P
Bramanti
Salvatore
S
Cuzzocrea
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002108:Ceruletide / Q000008:administration & dosage; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D016896:Treatment Outcome
D015415:Biomarkers; D005419:Flavonoids; D002108:Ceruletide; D048369:MAP Kinase Kinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one