Lysophosphatidylcholine activates transcription factor NF-kappaB and AP-1 in AR42J cells.
Phospholipase A2 (PLA2) has been suggested in the pathogenesis of acute pancreatitis, in part through the PLA2-generated phospholipid by-products, most notably lysophosphatidylcholine (lyso-PC). The effects of lyso-PC on pancreatic acinar cells other than necrosis are poorly characterized. Recent studies have suggested a role of the activation of transcription factors such as nuclear factor kappa B (NF-kappaB) for the pathogenesis of acute pancreatitis. Here we examined the effects of lyso-PC on the activation of transcriptional factors in rat pancreatic AR42J cells. Lyso-PC induced apoptosis at concentrations > or = 10 microM. At 10 and 25 microM, lyso-PC increased the NF-kappaB- and activator protein-1 (AP-1)-specific DNA binding activity as determined by electrophoretic mobility shift assay. Lyso-PC also increased the transcriptional activity of NF-kappaB and AP-1 as assessed by luciferase assay. Lyso-PC increased the mRNA level of pancreatitis-associated protein-I and c-jun. Lyso-PC activated three classes of mitogen activated protein kinases: extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase/stress-activated protein kinase and p38 kinases. Activation of transcription factors by lyso-PC was not altered by a specific platelet activating factor receptor antagonist, TCV-309, suggesting that the activation was independent of the platelet activating factor receptor. These molecular events may suggest a novel role of lyso-PC for the modulation of acinar cell function.
Masamune
A
A
Department of Gastroenterology, Tohoku University School of Medicine, Sendai, Japan.
Sakai
Y
Y
Yoshida
M
M
Satoh
A
A
Satoh
K
K
Shimosegawa
T
T
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007546:Isoquinolines / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D016328:NF-kappa B / Q000502:physiology*; D010195:Pancreatitis / Q000503:physiopathology*; D000073718:Pancreatitis-Associated Proteins; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044005:Tetrahydroisoquinolines; D018808:Transcription Factor AP-1 / Q000502:physiology*
D007546:Isoquinolines; D008244:Lysophosphatidylcholines; D016328:NF-kappa B; D000073718:Pancreatitis-Associated Proteins; D010975:Platelet Aggregation Inhibitors; D011726:Pyridinium Compounds; C000612141:REG3A protein, human; D044005:Tetrahydroisoquinolines; D018808:Transcription Factor AP-1; C067430:TCV 309