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

A. Masamune, Y. Sakai, M. Yoshida, A. Satoh, K. Satoh, T. Shimosegawa

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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-κB) 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 ≥10 μM. At 10 and 25 μM, lyso-PC increased the NF-κB- 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-κB 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.

Original languageEnglish
Pages (from-to)1871-1881
Number of pages11
JournalDigestive Diseases and Sciences
Volume46
Issue number9
DOIs
Publication statusPublished - 2001 Sep 26

Keywords

  • AP-1
  • Acute pancreatitis
  • Lysophosphatidylcholine
  • MAP kinases
  • NF-κB
  • Phospholipase A2

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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