Nitric oxide and tumor necrosis factor-alpha production by Ixeris dentata in mouse peritoneal macrophages.

Using mouse peritoneal macrophages, we have examined the mechanism by which Ixeris dentata (IXD) regulates nitric oxide (NO) production. When IXD was used in combination with recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production. However, IXD had no effect on NO production by itself. The increased production of NO from rIFN-gamma plus IXD-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappa B (NF-kappaB). Furthermore, treatment with IXD alone or rIFN-gamma plus IXD in peritoneal macrophages caused a significant increase in tumor necrosis factor-alpha (TNF-alpha) production. PDTC decreased TNF-alpha production induced by IXD significantly. These findings demonstrate that IXD 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 IXD.