Wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, enhances LPS-induced NO production from murine peritoneal macrophages

Biochem Biophys Res Commun. 1997 Nov 26;240(3):692-6. doi: 10.1006/bbrc.1997.7722.


To elucidate the role of phosphatidylinositol-3-kinase (PI3K) during macrophage activation, we examined the effects of wortmannin, a specific inhibitor of PI3K, on the induction of nitric oxide (NO) synthesis and tumor necrosis factor-alpha (TNF-alpha) secretion from lipopolysaccharide (LPS)-stimulated macrophages. Wortmannin had no effects on NO synthesis and TNF-alpha secretion by itself. Wortmannin markedly potentiated the LPS-induced NO production in a dose-dependent manner. Western blot analysis demonstrated that significantly increased levels of iNOS protein were expressed in LPS-stimulated macrophages treated with wortmannin, compared to those without LPS. Furthermore, enhancement of TNF-alpha secretion was observed in the initiation stage for activation of LPS-stimulated macrophages treated with wortmannin. These results suggest that PI3K plays an important role in transducing the signal that is involved in LPS-induced macrophage activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology*
  • Animals
  • Blotting, Western
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / enzymology
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Signal Transduction / drug effects
  • Thioglycolates / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Wortmannin


  • Androstadienes
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Phosphoinositide-3 Kinase Inhibitors
  • Thioglycolates
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Wortmannin