Role of mitogen-activated protein kinases, NF-kappaB, and AP-1 on cerulein-induced IL-8 expression in pancreatic acinar cells.
The cholecystokine (CCK) analogue cerulein causes pathophysiological, morphological, and biochemical events similar to various aspects of human pancreatitis. Doses of CCK or cerulein beyond those that cause the maximum pancreatic secretion of amylase and lipase result in pancreatitis, which is characterized by a dysregulation of the digestive enzyme production and cytoplasmic vacuolization and the death of acinar cells, edema formation, and an infiltration of inflammatory cells into the pancreas. This study aims to investigate whether cerulein induces IL-8 expression in pancreatic acinar cells, and whether cerulein-induced IL-8 expression is inhibited in the cells transfected with mutant genes for c-jun (TAM-67), or IkappaBalpha (MAD-3) or treated inhibitors of mitogen-activated protein kinases (MAPKs). As a result, cerulein induced IL-expression, which was inhibited in the cells transfected with TAM-67 or MAD-3 or treated inhibitors of MAPK. In conclusion, activation of MAPK, nuclear factor-kappaB (NF-kappaB), and activator protein-1 (AP-1) may be the upstream signaling for cerulein-induced IL-8 expression in pancreatic acinar cells.
Ju
Kyung Don
KD
Department of Pharmacology, Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Yu
Ji Hoon
JH
Kim
Hyeyoung
H
Kim
Kyung Hwan
KH
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002108:Ceruletide / Q000494:pharmacology*; D017931:DNA Primers; D016209:Interleukin-8 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D017931:DNA Primers; D016209:Interleukin-8; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D018808:Transcription Factor AP-1; D002108:Ceruletide; D020928:Mitogen-Activated Protein Kinases