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 language | English |
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Pages (from-to) | 159-163 |
Number of pages | 5 |
Journal | Immunology Letters |
Volume | 77 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2001 Jul 2 |
Externally published | Yes |
Bibliographical note
Funding Information:We would like to thank Drs G. Trinchieri (Wistar Institute, USA), J.W. Lee (Chonnam National University, Korea) and Y.-K. Choe (KRIBB, Korea) for providing reagents. This work was supported by Grants from the KOSEF (IRC to Tae Sung Kim) and in part from the GenoCheck Co. Ltd (Ansan, Korea).
Keywords
- Interleukin-12
- Macrophage
- Nuclear factor-κB
- Parthenolide
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology