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Dendritic cell maturation stage determines susceptibility to the proteasome inhibitor bortezomib

Item Type:Article
Title:Dendritic cell maturation stage determines susceptibility to the proteasome inhibitor bortezomib
Creators Name:Subklewe, M. and Sebelin-Wulf, K. and Beier, C. and Lietz, A. and Mathas, S. and Doerken, B. and Pezzutto, A.
Abstract:The proteasome inhibitor bortezomib has been used successfully in the treatment of non-Hodgkin lymphomas in humans, and in the treatment of graft versus host disease (GVHD) and autoimmune diseases in animal models. The mechanism of growth inhibition and immunosuppression is only partly understood. Here, we have evaluated the differential effect of bortezomib on human monocyte derived immature and mature dendritic cells (DCs) as the maturation stage of DCs determines their function. We found bortezomib to induce apoptotic cell death in immature DCs and to a much lesser extent, in mature DCs. Furthermore, cytokine-induced maturation of immature DCs was inhibited by bortezomib, whereas already matured DCs remained unaffected as seen by phenotype and allostimulatory capacity. This corresponded to a decreased NF-kappaB activity in immature DCs, whereas NF-kappaB activity of mature DCs was not affected. In conclusion, our data expand on previous reports on the effects of proteasome inhibitors on human monocyte-derived DCs by demonstrating a differential effect of bortezomib on immature versus mature DCs. Our findings suggest a potential role of bortezomib in modulating immune responses in humans through inhibition of DC maturation.
Keywords:dendritic cells, Maturation, Proteasome Inhibition, NF-kappaB
Source:Human Immunology
ISSN:0198-8859
Publisher:Elsevier (The Netherlands)
Volume:68
Number:3
Page Range:147-155
Date:March 2007
Official Publication:https://doi.org/10.1016/j.humimm.2006.12.005
PubMed:View item in PubMed

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