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.
Chung
Hwan-Suck
HS
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Chonbuk 570-749, South Korea.
Jeong
Hyun-Ja
HJ
Kim
Jung-Soo
JS
Jeong
Seung-Il
SI
Kim
Kyung-Soo
KS
Kim
Kang-San
KS
Kang
Byung-Ki
BK
Ahn
Jong-Woong
JW
Baek
Seung-Hwa
SH
Kim
Hyung-Min
HM
D000818:Animals; D015153:Blotting, Western; D004731:Endotoxins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D029756:Euonymus / Q000737:chemistry*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004731:Endotoxins; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D016328:NF-kappa B; D010936:Plant Extracts; D011759:Pyrrolidines; D011994:Recombinant Proteins; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse