title: Involvement of nuclear factor-kappaB in the inhibition of interleukin-12 production from mouse macrophages by baicalein, a flavonoid in Scutellaria baicalensis.
abstract: Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy for preventing development and progression of disease in experimental models of autoimmunity. In this study we investigated the effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). Baicalein potently inhibited the LPS-induced IL-12 production from both primary macrophages and RAW264.7 monocytic cell-line in a dose-dependent manner (the IC50 values were 43.7 and 17.4 microM, respectively). The effect of baicalein on IL-12 gene promoter activation was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs. The repressive effect mapped to a region in the IL-12 gene promoter containing a binding site for NF-kappaB. Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF-kappaB site, which significantly decreased upon addition of baicalein, indicating that baicalein inhibited IL-12 production in LPS-activated macrophages via inhibition of NF-kappaB binding activity.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju, Republic of Korea.
authors.forename: Bok Yun
authors.initials: BY
authors.lastname: Kang
authors.forename: Su Wol
authors.initials: SW
authors.lastname: Chung
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D020128:Inhibitory Concentration 50; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000378:metabolism*; D008517:Phytotherapy; D018517:Plant Roots; D020133:Reverse Transcriptase Polymerase Chain Reaction; D031364:Scutellaria baicalensis; D013047:Specific Pathogen-Free Organisms; D014162:Transfection
chemical_list: D017931:DNA Primers; D044950:Flavanones; D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018664:Interleukin-12; C006680:baicalein