Suppression of interleukin-6 production in macrophages by furonaphthoquinone NFD-37.
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)-kappaB activation has been shown to play a key role in LPS-induced IL-6 expression, the effect of NFD-37 on LPS-induced NF-kappaB activation was further analyzed. NFD-37 exhibited a dose-dependent inhibitory effect on LPS-induced phosphorylation of inhibitory kappaB alpha protein (IkappaB alpha), and subsequently inhibited LPS-induced IkappaB alpha degradation as well as NF-kappaB transcriptional activity. In another experiment, NFD-37 inhibited both IL-6 promoter activity and NF-kappaB transcriptional activity elicited by an expression vector encoding IkappaB kinase beta. Taken together, NFD-37 down-regulated LPS-induced IL-6 expression through NF-kappaB activation, which could provide a pharmacological basis for the anti-inflammatory properties of furonaphthoquinone analogs.
Shin
Hyun-Mo
HM
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Lee
Yong Rok
YR
Chang
Yoon Sook
YS
Lee
Jun-Young
JY
Kim
Byung Hak
BH
Min
Kyung Rak
KR
Kim
Youngsoo
Y
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C505240:2-methyl-2-(2-methylpropenyl)-2,3-dihydronaphtho(2,3-b)furan-4,9-dione; D005663:Furans; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009285:Naphthoquinones; C000606205:Nfkbia protein, mouse; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse