The anti-inflammatory sesquiterpene lactone parthenolide suppresses IL-4 gene expression in peripheral blood T

Sesquiterpene lactones (SL) derived from Mexican India medicinal plants and parthenolide, the major SL from European feverfew, have raised considerable interest because of their anti-inflammatory and complex pharmacological action. Interleukin-4 (IL-4) is a key cytokine that influences the developme...

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Bibliographic Details
Published in:European journal of immunology 2002-12, Vol.32 (12), p.3587-3597
Main Authors: Li-Weber, Min, Giaisi, Marco, Treiber, Monika K, Krammer, Peter H
Format: Article
Language:English
Subjects:
Adult
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Binding Sites - genetics
Down-Regulation - drug effects
Humans
In Vitro Techniques
Interferon-gamma - genetics
Interleukin-2 - genetics
Interleukin-4 - genetics
Interleukin-4 - metabolism
Jurkat Cells
Lymphocyte Activation
NF-kappa B - metabolism
Plants, Medicinal
Promoter Regions, Genetic - drug effects
Protein Binding - drug effects
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sesquiterpenes - pharmacology
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Transcription, Genetic - drug effects
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Summary:Sesquiterpene lactones (SL) derived from Mexican India medicinal plants and parthenolide, the major SL from European feverfew, have raised considerable interest because of their anti-inflammatory and complex pharmacological action. Interleukin-4 (IL-4) is a key cytokine that influences the development of T helper 2 cells and plays an important role in the pathogenesis of allergic diseases. We show here that the anti-inflammatory parthenolide suppresses IL-4 expression at the mRNA and the protein levels in a dose-dependent manner. We demonstrate that parthenolide blocks NF-kappaB binding to two important IL-4 promoter regulatory elements and suppresses promoter activity upon T cell activation. Differences regarding the effects of parthenolide on expression levels of IL-4, IL-2 and IFN-gamma were observed. Parthenolide (2.5 microM) could completely suppress IL-4 protein levels secreted in anti-CD3/CD28-stimulated peripheral blood T cells from allergic and normal donors. Complete inhibition of IL-2 and IFN-gamma requires higher doses of parthenolide. So far, drugs directed against IL-4 expression have not been described. This finding raises the potential to develop parthenolide to treat IL-4-mediated allergic-like inflammation.
ISSN:0014-2980