Red ginseng acidic polysaccharide (RGAP) in combination with IFN-gamma results in enhanced macrophage function through activation of the NF-kappaB 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-alpha) and reactive oxygen species (ROS) production were not changed by RGAP. However, treatment of macrophages with a combination of RGAP and recombinant interferon-gamma (rIFN-gamma) enhanced killing of tumor cells. In addition, the combination treatment showed marked cooperative induction of IL-1, IL-6, TNF-alpha, and NO production. Electrophoretic mobility shift assay analysis revealed that treatment of macrophages with RGAP plus rIFN-gamma induced the activation of the nuclear factor-kappa B (NF-kappaB) transcription factor. In agreement with this, the combination treatment resulted in increased NF-kappaB-p65 expression. The present results demonstrate synergistic effects on macrophage function of RGAP in combination with rIFN-gamma, and suggest that NF-kappaB plays an important role in mediating these effects. These data also support the development of clinical studies of this combination.
Choi
Hye-Sook
HS
Division of Immunopharmacology, College of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, Republic of Korea.
Kim
Kyung-Ho
KH
Sohn
Eunwha
E
Park
Jong-Dae
JD
Kim
Byung-Oh
BO
Moon
Eun-Yi
EY
Rhee
Dong-Kwon
DK
Pyo
Suhkneung
S
D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide; D005894:Panax / Q000737:chemistry*; D010587:Phagocytosis; D011134:Polysaccharides / Q000494:pharmacology*
D016207:Cytokines; D016328:NF-kappa B; D011134:Polysaccharides; D009569:Nitric Oxide; D007371:Interferon-gamma