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

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.