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学科主题: 临床医学
题名:
Bortezomib regulates the chemotactic characteristics of T cells through downregulation of CXCR3/CXCL9 expression and induction of apoptosis
作者: 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
发表日期: 2012-12-01
DOI: 10.1007/s12185-012-1195-6
卷: 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
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
项目资助者: National Natural Science Foundation of China ; China National Key Technology RD Program
WOS记录号: WOS:000312876200014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66501
Appears in Collections:北京大学第一临床医学院_血液内科_期刊论文

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作者单位: Peking Univ, Hosp 1, Dept Hematol, Beijing 100034, Peoples R China

Recommended Citation:
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.
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