Inhibition of interleukin-12 production in lipopolysaccharide-activated mouse macrophages by parthenolide, a predominant sesquiterpene lactone in Tanacetum parthenium: involvement of nuclear factor-kappaB.
Pharmacological control of interleukin-12 (IL-12) production may be a key therapeutic strategy for modulating immunological diseases dominated by type-1 cytokine responses. In this study, we investigated the effects of parthenolide, an anti-inflammatory sesquiterpene, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). Parthenolide potently inhibited the LPS-induced IL-12 production in a dose-dependent manner. The effect of parthenolide on IL-12 p40 promoter activation was analyzed by transfecting RAW264.7 monocytic cells with p40 promoter/luciferase constructs. The repressive effect mapped to a region in the p40 promoter containing a binding site for nuclear factor-kappaB (p40-kappaB). Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the kappaB site, which significantly decreased upon addition of parthenolide. These results suggest that parthenolide-induced inhibition of IL-12 production in macrophages may explain some of the biological effects of parthenolide including its anti-inflammatory activity.
Kang
B Y
BY
College of Pharmacy, Chonnam National University, 500-757, Kwangju, South Korea.
Chung
S W
SW
Kim
T S
TS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000378:metabolism*; D010946:Plants, Medicinal; D011401:Promoter Regions, Genetic; D012717:Sesquiterpenes / Q000494:pharmacology*; D020903:Tanacetum parthenium; D014162:Transfection
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; D018664:Interleukin-12; C002669:parthenolide