Activation of inducible nitric oxide synthase by Euonymus alatus in mouse peritoneal macrophages

Clin Chim Acta. 2002 Apr;318(1-2):113-20. doi: 10.1016/s0009-8981(01)00808-7.

Abstract

Background: Euonymus alatus (EA) has been used for tumor therapy. However, it is still unclear how this herb prevents the diseases in experimental models. Nitric oxide (NO) as a potent macrophage-derived effector molecule against a variety of tumors has received increasing attention.

Methods: Using mouse peritoneal macrophages, we have examined the mechanism by which EA regulates NO production.

Results: When EA was used in combination with recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production. However, EA had no effect on NO production by itself. The increased production of NO from rIFN-gamma plus EA-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappa B (NF-kappaB). Furthermore, treatment of peritoneal macrophages with rIFN-gamma plus EA caused a significant increase in tumor necrosis factor-alpha (TNF-alpha) production. PDTC also decreased the effects of EA on TNF-alpha production significantly.

Conclusions: EA increases the production of NO and TNF-alpha by rIFN-gamma-primed macrophages and suggest that NF-kappaB plays a critical role in mediating these effects of EA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Endotoxins / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Induction / drug effects
  • Enzyme Inhibitors / pharmacology
  • Euonymus / chemistry*
  • In Vitro Techniques
  • Indicators and Reagents
  • Interferon-gamma / pharmacology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / enzymology*
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Plant Extracts / antagonists & inhibitors
  • Plant Extracts / pharmacology
  • Pyrrolidines / pharmacology
  • Recombinant Proteins
  • Signal Transduction / drug effects
  • Thiocarbamates / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • omega-N-Methylarginine / pharmacology

Substances

  • Endotoxins
  • Enzyme Inhibitors
  • Indicators and Reagents
  • NF-kappa B
  • Plant Extracts
  • Pyrrolidines
  • Recombinant Proteins
  • Thiocarbamates
  • Tumor Necrosis Factor-alpha
  • pyrrolidine dithiocarbamic acid
  • omega-N-Methylarginine
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse