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

Degradation of IkappaB (IKB) 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 IKB degradation in RAW264.7 murine macrophages. IKB degradation was notably suppressed by l'-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 IKB degradation, while other chemopreventive agents use alternative pathway(s) to suppress the expression of proinflammatory genes. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.