Lysophosphatidylcholine activates transcription factor NF-kappa B and AP-1in AR42J cells

Phospholipase A(2) (PLA(2)) has been suggested in the pathogenesis of acute pancreatitis, in part through the PLA(2)-generated phospholipid by-product s, most notably lysophosphatidylcholine (lyso-PC). The effects of lyso-PC o n pancreatic acinar cells other than necrosis are poorly characterized. Rec ent studies have suggested a role of the activation of transcription factor s 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 apop tosis at concentrations greater than or equal to 10 muM. At 10 and 25 muM, iyso-PC increased the NF-kappaB- and activator protein-1 (AP-1)-specific DN A binding activity as determined by electrophoretic mobility shift assay. L yso-PC also increased the transcriptional activity of NF-kappaB and AP-1 as assessed by luciferase assay. Lyso-PC increased the mRNA level of pancreat itis-associated protein-I and c-jun. Lyso-PC activated three classes of mit ogen 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 specifi c 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 modulati on of acinar cell function.