title: Bortezomib inhibits bone marrow-derived dendritic cells.
abstract: Graft versus-host disease (GVHD) severely limits the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treating leukemia. Dendritic cells (DCs) are critical for the development. Here, we examined the effect of proteasome inhibitor Bortezomib on DCs in vitro. Primary cultured mouse DCs were treated with Bortezomib and their proliferation was observed. The expression of CD80 and CD86 and cytokine secretion of LPS-activated DCs was also quantified under Bortezomib. The ability of DCs to activate T cells was also measured by the mixed lymphocyte reaction assay. Finally the effect of Bortezomib on nuclear translocation of NF-κB was measured by EMSA. Bortezomib can inhibit the proliferation of DCs in a dose- and time-dependent manner. It also blocked the expression of co-receptors CD80 and CD86 and secretion of cytokines IL-12 and TNF-α in DCs treated with LPS. Mixed lymphocyte reaction assay suggested Bortezomib reduced the ability of DCs to activate T cells. Finally, we found Bortezomib can inhibit the nuclear translocation of NF-κB in DCs. Our findings indicated that Bortezomib blocked the functions of DCs in various aspects, and is a potential drug candidate for GVHD.
authors.affiliation: Department of Internal Medicine, First Hospital Affiliated to Suzhou University China ; Department of Internal Medicine, Lianyungang First People's Hospital China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Biology and Medical Sciences to Suzhou University China ; Department of Biological Treatment of Tumor Cells, Huai'an Second People's Hospital Huai'an, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Internal Medicine, First Hospital Affiliated to Suzhou University China ; Department of Biological Treatment of Tumor Cells, Huai'an Second People's Hospital Huai'an, China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, First Hospital Affiliated to Suzhou University China.
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.affiliation: Institute of Biology and Medical Sciences to Suzhou University China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D000069286:Bortezomib / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D061988:Proteasome Inhibitors; D000069286:Bortezomib
keywords: Bortezomib; T cell activation; dendritic cells; graft versus-host disease; nuclear factor-κB