Alcohol-Fermented Soybean Increases the Expression of Receptor-Interacting Protein 2 and IκB Kinase β in Mouse Peritoneal Macrophages

Soybean is a useful component of traditional Korean medicine with well-documented health-promoting effects. We investigated the effects of alcohol-fermented soybean (AFS) on immune function. When AFS treatment was used in combination with recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha production in mouse peritoneal macrophages. AFS increased the expression of inducible NO synthase mRNA and protein in rIFN-gamma-primed macrophages. Treating macrophages with pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kappa B (NF-kappa B), decreased the synergistic effects of AFS. In addition, AFS in combination with rIFN-gamma increased the phosphorylation of p38 and c-Jun N-terminal kinase (INK) but not extracellular signal-regulated kinase. However, AFS had no effect on phosphorylation of mitogen-activated protein kinases by itself. The p38 inhibitor SB203580 or the INK inhibitor SP600125 inhibited the AFS-induced NO and TNF-alpha production. When AFS was used in combination with rIFN-gamma, there was a co-operative activation of NF-kappa B and receptor-interacting protein 2 (Rip2)/I kappa B kinase (IKK)-beta. Our results indicate that AFS increases the production of NO and TNF-alpha through the activation of Rip2/IKK-beta in rIFN-gamma-primed macrophages.