Involvement of nuclear factor-kappaB in the inhibition of interleukin-12 production from mouse macrophages by baicalein, a flavonoid in Scutellaria baicalensis.
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.
Kang
Bok Yun
BY
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju, Republic of Korea.
Chung
Su Wol
SW
Kim
Seung Hyun
SH
Cho
Daeho
D
Kim
Tae Sung
TS
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
D017931:DNA Primers; D044950:Flavanones; D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018664:Interleukin-12; C006680:baicalein