Red ginseng acidic polysaccharide (RGAP) in combination with IFN-γ results in enhanced macrophage function through activation of the NF-κB pathway

This study examined the effects of red ginseng acidic polysaccharide (RGAP) on macrophage-mediated cytotoxicity towards murine melanoma B16 cells. RGAP alone had no effect on killing of tumor cells. RGAP treatment increased the production of interleukin-1 (IL-1), IL-6, and nitric oxide (NO) by macrophages, whereas tumor necrosis factor (TNF-α) and reactive oxygen species (ROS) production were not changed by RGAP. However, treatment of macrophages with a combination of RGAP and recombinant interferon-γ (rIFN-γ) enhanced killing of tumor cells. In addition, the combination treatment showed marked cooperative induction of IL-1, IL-6, TNF-α, and NO production. Electrophoretic mobility shift assay analysis revealed that treatment of macrophages with RGAP plus rIFN-γ induced the activation of the nuclear factor-kappa B (NF-κB) transcription factor. In agreement with this, the combination treatment resulted in increased NF-κB-p65 expression. The present results demonstrate synergistic effects on macrophage function of RGAP in combination with rIFN-γ, and suggest that NF-κB plays an important role in mediating these effects. These data also support the development of clinical studies of this combination.