Expression of inducible nitric oxide synthase by Corydalis turtschaninovii on interferon-gamma stimulated macrophages.
OBJECTIVE
Corydalis turtschaninovii (CT) 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
In this study, using mouse peritoneal macrophages, we have examined the mechanism by which CT regulates NO production.


RESULTS
When CT was used in combination with recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production. However, CT had no effect on NO production by itself. The increase in NO synthesis was reflected as an increased amount of inducible NO synthase (iNOS) protein. The increased production of NO from rIFN-gamma plus CT-stimulated peritoneal macrophages was decreased by the treatment with N(G)-monomethyl-L-arginine or N(alpha)-Tosyl-Phe Chloromethyl Ketone, iNOS inhibitor. The increased production of NO from rIFN-gamma plus CT-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate, an inhibitor of nuclear factor kappa B (NF-kappaB). However, treatment of peritoneal macrophages with rIFN-gamma plus CT had no effect on the increase in tumor necrosis factor-alpha (TNF-alpha) production.


CONCLUSIONS
Our findings demonstrate that CT 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 CT.
An
Hyo-Jin
HJ
Department of Pharmacology, College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Dongdaemun-Gu, Seoul, Republic of Korea.
Rim
Hong-Kun
HK
Chung
Hwan-Suck
HS
Choi
In-Young
IY
Kim
Na-Hyung
NH
Kim
Su-Jin
SJ
Moon
Phil-Dong
PD
Myung
Noh-Yil
NY
Jeong
Hyun-Ja
HJ
Jeong
Chang-Hyun
CH
Chung
Seok-Hee
SH
Um
Jae-Young
JY
Hong
Seung-Heon
SH
Kim
Hyung-Min
HM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D031311:Corydalis; D004357:Drug Synergism; D007371:Interferon-gamma / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D011994:Recombinant Proteins; D013859:Thiocarbamates / Q000494:pharmacology
D000975:Antioxidants; D016328:NF-kappa B; D010936:Plant Extracts; D011759:Pyrrolidines; D011994:Recombinant Proteins; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II