The sesquiterpene lactone parthenolide inhibits LPS- but not TNF-α-induced maturation of human monocyte-derived dendritic cells by inhibition of the p38 mitogen-activated protein kinase pathway

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:110

Article

Uchi, H ; Arrighi, JF ; Aubry, JP ; Furue, M ; Hauser, C

关键词: dendritic cells;    maturation;    lipopolysaccharide;    signal transduction;   

DOI  :  10.1067/mai.2002.126381

来源: Elsevier

【 摘 要 】

Background: Dendritic cells (DCs) are the most potent antigenpresenting cells, and the manipulation of DC maturation provides a strategy for the treatment of allergic and inflammatory diseases. Objective: In this study we examined the effect of the anti-inflammatory sesquiterpene lactone parthenolide (PTL) on DC maturation induced by LPS or TNF-alpha. Methods: Human monocyte-derived DCs generated by means of culture with GM-CSF and IL-4 were pretreated with PTL and subsequently stimulated with LPS or TNF-alpha. Results: PTL inhibited the upregulation of CD80, CD83, CD86, CD40, and MHC class II; the allostimulatory function; the production of TNF-alpha and IL-12; and the downregulation of FITC-labeled dextran uptake in human monocyte-derived DCs stimulated with LPS but not with TNF-alpha. The inhibitory effect of PTL on DC maturation was preceded by inhibition of the phosphorylation of p38 mitogen-activated protein kinase but not the nuclear translocation of NF-kappaB. Conclusion: These results might offer PTL not only as a promising compound for the treatment of LPS-induced disorders, including sepsis or septic shock, by inhibition of excessive DC maturation but also as a tool to further dissect the signaling pathways involved in DC maturation.

【 授权许可】

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