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

• Published in: International immunopharmacology Vol. 6; no. 6; pp. 916 - 923
• Main Authors: Shin, Hyun-Mo, Lee, Yong Rok, Chang, Yoon Sook, Lee, Jun-Young, Kim, Byung Hak, Min, Kyung Rak, Kim, Youngsoo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.06.2006; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell Line; Dose-Response Relationship, Drug; Furans - pharmacology; Furonaphthoquinone; Gene Expression - drug effects; I-kappa B Kinase - genetics; I-kappa B Kinase - metabolism; I-kappa B Proteins - genetics; I-kappa B Proteins - metabolism; IL-6 production; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lipopolysaccharides - pharmacology; Macrophages; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Naphthoquinones - pharmacology; NF-kappa B - genetics; NF-kappa B - metabolism; NF-kappa B p50 Subunit - genetics; NF-kappa B p50 Subunit - metabolism; NF-KappaB Inhibitor alpha; NF-κB activation; Pharmacology. Drug treatments; Phosphorylation - drug effects; Promoter Regions, Genetic - drug effects; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Transfection; IL-6 production; NF-κB activation; Furonaphthoquinone; Macrophages; Interleukin 6; Signal transduction; Cytokine; Production; NF-KB activation; Activation; Transcription factor NFκB; Macrophage
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2006.01.006

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.