title: The anti-inflammatory sesquiterpene lactone parthenolide suppresses IL-4 gene expression in peripheral blood T.
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-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.
authors.affiliation: Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany. m.li-weber@dkfz-heidelberg.de
authors.forename: Min
authors.initials: M
authors.lastname: Li-Weber
authors.forename: Marco
authors.initials: M
authors.lastname: Giaisi
authors.forename: Monika K
authors.initials: MK
authors.lastname: Treiber
authors.forename: Peter H
authors.initials: PH
authors.lastname: Krammer
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001665:Binding Sites / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism; D010946:Plants, Medicinal; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007376:Interleukin-2; D016328:NF-kappa B; D012333:RNA, Messenger; D012717:Sesquiterpenes; D015847:Interleukin-4; C002669:parthenolide; D007371:Interferon-gamma