CancerB increases production of nitric oxide and tumor necrosis factor-alpha in peritoneal macrophages.
BACKGROUND
CancerB (CCB, IMSF-5), herbal combination, may be able to stimulate potential toxic mediators such as nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) in isolated mouse peritoneal macrophages.


METHODS
NO production was determined by Griess method, and TNF-alpha production by enzyme-linked immunosorbent assay. Amounts of proteins were observed by Western blotting.


RESULTS
CCB had no effect on NO production by itself, but CCB alone did stimulate the production of TNF-alpha. When CCB was used in combination with recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production, TNF-alpha production and NF-kappa B activation. The increase in NO synthesis was reflected as an increased amount of inducible NO synthase protein. The increased production of NO from rIFN-gamma plus CCB-stimulated peritoneal macrophages was decreased by the treatment with N(G)-monomethyl-L-arginine or N(alpha)-Tosyl-Phe Chloromethyl Ketone. Nuclear factor-kappa B (NF-kappa B) inhibitor, pyrrolidine dithiocarbamate was able to completely inhibit the production of NO and TNF-alpha.


CONCLUSIONS
These findings demonstrate that CCB increases the production of NO and TNF-alpha by rIFN-gamma-primed peritoneal macrophages and suggest that NF-kappa B plays a critical role in mediating these effects of CCB.
Jeong
Hyun-Ja
HJ
Department of Oriental Pharmacy, College of Pharmacy, Korea Institute of Oriental Pharmacy, Wonkwang University, Iksan, Chonbuk, 570-749, Republic of Korea.
Chung
Hwan-Suck
HS
Hong
Seung-Heon
SH
Na
Ho-Jeong
HJ
Koo
Hye-Young
HY
Seo
Sang-Bong
SB
Kim
Kyung-Suk
KS
Song
Yung-Sun
YS
Kim
Hyung-Min
HM
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D029001:Herbal Medicine; D007371:Interferon-gamma / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008518:Medicine, East Asian Traditional; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D011994:Recombinant Proteins; D013859:Thiocarbamates / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D011759:Pyrrolidines; D011994:Recombinant Proteins; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D014108:Tosylphenylalanyl Chloromethyl Ketone; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase