Suppression of interleukin-6 production in macrophages by furonaphthoquinone NFD-37

Abstract

Furonaphthoquinone compounds have been reported to exhibit anticancer, antibacterial and antiviral properties. The molecular basis for these diverse properties is not known. 2-Methyl-2-(2-methylpropenyl)-2,3-dihydronaphthoquinone [2,3- b]furan-4,9-dione (NFD-37) is a synthetic furonaphthoquinone compound. In the present study, NFD-37 was found to inhibit interleukin (IL)-6 production in lipopolysaccharide (LPS)-stimulated murine macrophages RAW 264.7. Further, NFD-37 attenuated LPS-induced synthesis of IL-6 transcript but also inhibited LPS-induced IL-6 promoter activity. Since nuclear factor (NF)-κB activation has been shown to play a key role in LPS-induced IL-6 expression, the effect of NFD-37 on LPS-induced NF-κB activation was further analyzed. NFD-37 exhibited a dose-dependent inhibitory effect on LPS-induced phosphorylation of inhibitory κBα protein (IκBα), and subsequently inhibited LPS-induced IκBα degradation as well as NF-κB transcriptional activity. In another experiment, NFD-37 inhibited both IL-6 promoter activity and NF-κB transcriptional activity elicited by an expression vector encoding IκB kinase β. Taken together, NFD-37 down-regulated LPS-induced IL-6 expression through NF-κB activation, which could provide a pharmacological basis for the anti-inflammatory properties of furonaphthoquinone analogs.