Nitric oxide and tumor necrosis factor-α 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-γ (rIFN-γ), 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-γ plus IXD-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappa B (NF-κB). Furthermore, treatment with IXD alone or rIFN-γ plus IXD in peritoneal macrophages caused a significant increase in tumor necrosis factor-α (TNF-α) production. PDTC decreased TNF-α production induced by IXD significantly. These findings demonstrate that IXD increases the production of NO and TNF-α by rIFN-γ-primed macrophages and suggest that NF-κB plays a critical role in mediating these effects of IXD.