Effects of selected food factors with chemopreventive properties on combined lipopolysaccharide- and interferon-gamma-induced IkappaB degradation in RAW264.7 macrophages.

Degradation of IkappaB (IkappaB) is a key step for nuclear factor-kappaB (NF-kappaB)-induced transcription of certain proinflammatory genes, including inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. We selected seven chemopreventive agents and examined their effects on combined lipopolysaccharide- and interferon-gamma-induced IkappaB degradation in RAW264.7 murine macrophages. IkappaB degradation was notably suppressed by 1'-acetoxychavicol acetate (ACA), zerumbone (ZER), and benzylisothiocyanate (BITC), however, not by auraptene (AUR), while the suppressive potencies of nobiletin (NOB), genistein (GEN), and resveratrol (RES) were low, but significant. These results suggest that ACA, ZER, and BITC suppress iNOS/COX-2 gene expression mainly by attenuating IkappaB degradation, while other chemopreventive agents use alternative pathway(s) to suppress the expression of proinflammatory genes.