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

• Verfasst von: Li-Weber, Min [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: The anti-inflammatory sesquiterpene lactone parthenolide suppresses IL-4 gene expression in peripheral blood T cells
• Verf.angabe: Min Li‐Weber, Marco Giaisi, Monika K. Treiber and Peter H. Krammer
• E-Jahr: 2002
• Jahr: 28 November 2002
• Umfang: 11 S.
• Teil: volume:32
• Teil: year:2002
• Teil: number:12
• Teil: pages:3587-3597
• Teil: extent:11
• Fussnoten: Gesehen am 15.04.2021
• Titel Quelle: Enthalten in: European journal of immunology
• Ort Quelle: Weinheim : Wiley-VCH, 1971
• Jahr Quelle: 2002
• Band/Heft Quelle: 32(2002), 12, Seite 3587-3597
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/1521-4141(200212)32:12<3587::AID-IMMU3587>3.0.CO;2-E
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Allergy
• Sach-SW: IFN-γ
• Sach-SW: IL-2
• Sach-SW: IL-4
• Sach-SW: NF-κB
• K10plus-PPN: 1754979025

Abstract

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-κB 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-γ were observed. Parthenolide (2.5 μM) 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-γ 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.