Induction of cyclo-oxygenase-2 expression by methyl arachidonyl fluorophosphonate in murine J774 macrophages: Roles of protein kinase C, ERKs and p38 MAPK

Wan W. Lin, Bing C. Chen

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

1. Methyl arachidonyl fluorophosphonate (MAFP), an inhibitor of phospholipase A2 (PLA2), has been widely used to assess the roles of PLA2 in various cell functions. Here, we report on a novel action of this compound at concentrations similar to those used for PLA2 inhibition. 2. The murine macrophage J774 released a large amount of prostaglandin E2 (PGE2) by MAFP (1-30 μM), which was abolished by indomethacin and NS-398 but not by valeryl salicylate, and results from increased cyclo-oxygenase-2 (COX-2) protein levels and gene expression. 3. This PGE2 release was blocked by inhibitors of tyrosine kinase (genistein), protein kinase C (PKC) (Ro 31-8220, Go 6976 or LY 379196), mitogen-activated protein kinase kinase (MEK) (PD 098059) or p38 mitogen-activated protein kinase (MAPK) (SB 203580). 4. Consistent with these results, MAFP caused membrane translocation of PKCβI and βII isoforms and activated extracellular signal-regulated kinase (ERK) and p38 MAPK. 5. In accordance with these effects of MAFP, PKC activator phorbol 12-myristate 13-acetate (PMA) increased PGE2 release and caused activation of PKCβ, ERKs and p38 MAPK. 6. This is the first report that the PLA2 inhibitor, MAFP, can induce COX-2 gene expression and PGE2 synthesis via the PKC-, ERK- and p38 MAPK-dependent pathways. Thus, the use of MAFP as a PLA2 inhibitor should be treated with caution.

Original languageEnglish
Pages (from-to)1419-1425
Number of pages7
JournalBritish Journal of Pharmacology
Volume126
Issue number6
Publication statusPublished - 1999
Externally publishedYes

Keywords

  • COX-2 expression
  • ERK
  • J774 macrophage
  • MAFP
  • P38 MAPK
  • PKC

ASJC Scopus subject areas

  • Pharmacology

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