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.
Copyright 2002 Elsevier Science B.V.