Inhibition of interleukin-12 production in lipopolysaccharide-activated mouse macrophages by parthenolide, a predominant sesquiterpene lactone in Tanacetum parthenium

Involvement of nuclear factor-κB

B. Y. Kang, S. W. Chung, Tae Sung Kim

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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-κB (p40-κB). Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the κB 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.

Original languageEnglish
Pages (from-to)159-163
Number of pages5
JournalImmunology Letters
Volume77
Issue number3
DOIs
Publication statusPublished - 2001 Jul 2
Externally publishedYes

Fingerprint

Tanacetum parthenium
Sesquiterpenes
Lactones
Interleukin-12
Lipopolysaccharides
Macrophages
Anti-Inflammatory Agents
Macrophage Activation
Immune System Diseases
Luciferases
parthenolide
Binding Sites
Pharmacology
Cytokines
adjuvant P40

Keywords

  • Interleukin-12
  • Macrophage
  • Nuclear factor-κB
  • Parthenolide

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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title = "Inhibition of interleukin-12 production in lipopolysaccharide-activated mouse macrophages by parthenolide, a predominant sesquiterpene lactone in Tanacetum parthenium: Involvement of nuclear factor-κB",
abstract = "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-κB (p40-κB). Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the κB 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.",
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