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Bortezomib regulates the chemotactic characteristics of T cells through downregulation of CXCR3/CXCL9 expression and induction of apoptosis
Liu, Wei; Ren, Han-Yun; Dong, Yu-Jun; Wang, Li-Hong; Yin, Yue; Li, Yuan; Qiu, Zhi-Xiang; Cen, Xi-Nan; Shi, Yong-Jin
关键词Bortezomib T lymphocyte Chemokine Chemokine receptor Apoptosis
刊名INTERNATIONAL JOURNAL OF HEMATOLOGY
2012-12-01
DOI10.1007/s12185-012-1195-6
96期:6页:764-772
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Hematology
资助者National Natural Science Foundation of China ; China National Key Technology RD Program ; National Natural Science Foundation of China ; China National Key Technology RD Program
研究领域[WOS]Hematology
关键词[WOS]VERSUS-HOST-DISEASE ; PROTEASOME INHIBITOR BORTEZOMIB ; NON-HODGKINS-LYMPHOMA ; NF-KAPPA-B ; CHEMOKINE RECEPTORS ; FAMILY REGULATION ; MULTIPLE-MYELOMA ; GENE-EXPRESSION ; TUMOR-CELLS ; PHASE-II
英文摘要

The chemotactic movement of T lymphocytes mediated by chemokines and their receptors plays an important role in the pathogenesis of graft-versus-host disease (GVHD) post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). CCR7 and CXCR3 are two receptors associated with the development of GVHD. Bortezomib, a proteasome inhibitor, was recently found to prevent GVHD in a mouse model and to decrease the production of Th1 cytokines. Here, we report that bortezomib differentially regulates the expression of CXCR3 and CCR7 on T cells; it significantly decreases CXCR3 expression on T cells as well as its CD4(+)/CD8(+) subsets in a dose-dependent manner, while it does not significantly affect CCR7 expression on T cells and subsets. Moreover, the secretion of CXCL9 by activated T cells is also increasingly downregulated with increasing concentrations of bortezomib. Meanwhile, bortezomib inhibits T-cell chemotactic movements toward CXCL9 in a dose-dependent manner, but has no effect on CCL19-induced T-cell chemotaxis. Additionally, it was found that bortezomib treatment also prompts T-lymphocyte apoptosis through activation of caspase-3 and its downstream PARP cleavage in a dose- and time-dependent manner. These results suggest that bortezomib may act as a suppressor of GVHD by downregulating T-cell chemotatic movement toward GVHD target organs, as well as by inducing apoptosis.

语种英语
所属项目编号30940030 ; 81070448 ; 2008BAI61B01
资助者National Natural Science Foundation of China ; China National Key Technology RD Program ; National Natural Science Foundation of China ; China National Key Technology RD Program
WOS记录号WOS:000312876200014
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66501
专题北京大学第一临床医学院_血液内科
作者单位Peking Univ, Hosp 1, Dept Hematol, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Liu, Wei,Ren, Han-Yun,Dong, Yu-Jun,et al. Bortezomib regulates the chemotactic characteristics of T cells through downregulation of CXCR3/CXCL9 expression and induction of apoptosis[J]. INTERNATIONAL JOURNAL OF HEMATOLOGY,2012,96(6):764-772.
APA Liu, Wei.,Ren, Han-Yun.,Dong, Yu-Jun.,Wang, Li-Hong.,Yin, Yue.,...&Shi, Yong-Jin.(2012).Bortezomib regulates the chemotactic characteristics of T cells through downregulation of CXCR3/CXCL9 expression and induction of apoptosis.INTERNATIONAL JOURNAL OF HEMATOLOGY,96(6),764-772.
MLA Liu, Wei,et al."Bortezomib regulates the chemotactic characteristics of T cells through downregulation of CXCR3/CXCL9 expression and induction of apoptosis".INTERNATIONAL JOURNAL OF HEMATOLOGY 96.6(2012):764-772.
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