Phosphatidylinositol 3-kinase activity negatively regulates stability of cyclooxygenase 2 mRNA.

Academic Article

Abstract

  • Human alveolar macrophages have both lipopolysaccharide (LPS)-induced and constitutive phosphatidylinositol 3-kinase (PI3K) activity. We observed that blocking PI3K activity increased release of prostaglandin E2 after LPS exposure, and increasing PI3K activity (interleukin-13) decreased release of prostaglandin E2 after LPS exposure. This was not because of an effect of PI3K on phospholipase 2 activity. PI3K inhibition resulted in an increase in cyclooxygenase 2 (COX2) protein, mRNA, and mRNA stability. PI3K negatively regulated activation of the p38 pathway (p38, MKK3/6, and MAPKAP2), and an active p38 was necessary for COX2 production. The data suggest that PI3K inhibition of p38 modulates COX2 expression via destabilization of LPS-induced COX2 mRNA.

    • Authors

    Published In

    Keywords

  • Animals, Cells, Cultured, Cyclooxygenase 2, Dactinomycin, Dinoprostone, Enzyme Activation, Enzyme Inhibitors, Gene Expression Regulation, Enzymologic, Humans, Interleukin-13, Isoenzymes, Lipopolysaccharides, MAP Kinase Kinase 3, Membrane Proteins, Mice, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Models, Biological, Phosphatidylinositol 3-Kinases, Prostaglandin-Endoperoxide Synthases, Protein-Tyrosine Kinases, RNA Stability, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, p38 Mitogen-Activated Protein Kinases

    • Digital Object Identifier (doi)

    Pubmed Id

  • 12899488

    • Author List

  • Monick MM; Robeff PK; Butler NS; Flaherty DM; Carter AB; Peterson MW; Hunninghake GW

    • Start Page

  • 32992

    • End Page

  • 33000

    • Volume

  • 277

    • Issue

  • 36