Wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, enhances LPS-induced NO production from murine peritoneal macrophages.
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.
Park
Y C
YC
Department of Molecular Biology, Pusan National University, Korea.
Lee
C H
CH
Kang
H S
HS
Chung
H T
HT
Kim
H D
HD
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013864:Thioglycolates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha; D000077191:Wortmannin