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学科主题: 基础医学
题名:
The CKLF1-C19 peptide attenuates allergic lung inflammation by inhibiting CCR3- and CCR4-mediated chemotaxis in a mouse model of asthma
作者: Tian, L.1,2; Li, W.3; Wang, J.3,4; Zhang, Y.1,2; Zheng, Y.1,2; Qi, H.1,2; Guo, X.1,2; Zhang, Y.1,2; Ma, D.1,2; Shen, H.3; Wang, Y.1,2
关键词: asthma ; CCR3 ; CCR4 ; CKLF1 ; peptide
刊名: ALLERGY
发表日期: 2011-02-01
DOI: 10.1111/j.1398-9995.2010.02478.x
卷: 66, 期:2, 页:287-297
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Allergy ; Immunology
研究领域[WOS]: Allergy ; Immunology
关键词[WOS]: CHEMOKINE-LIKE FACTOR-1 ; MACROPHAGE-DERIVED CHEMOKINE ; UNRESTRAINED GUINEA-PIGS ; AIRWAY MUCUS PRODUCTION ; CHRONIC FUNGAL ASTHMA ; PULMONARY-FIBROSIS ; EOTAXIN EXPRESSION ; MOLECULAR-CLONING ; FUNCTIONAL LIGAND ; HUMAN EOSINOPHIL
英文摘要:

P>Background:

Human chemokine-like factor 1 (CKLF1) is a functional ligand for human CCR4, which is highly expressed on Th2 lymphocytes and plays an important role in the pathogenesis of asthma. The expression and function of CKLF1 are associated with asthma. The CKLF1 C-terminal peptides C19 and C27 also interact with human CCR4. Albeit with weaker chemotactic activity, C19 can inhibit chemotaxis induced by both CKLF1 and CCL17. Here, we explore whether C19 can act as an antagonist in the development of asthma.

Methods:

A mouse model of asthma and in vitro and in vivo chemotaxis assays were used.

Results:

Using a mouse model of asthma, we demonstrate here that C19 reduces airway eosinophilia, lung inflammation and airway hyperresponsiveness; in contrast, C27 has little effect on these parameters. The inhibitory effects of C19 on CCR4-mediated chemotaxis could be observed in human Th2 lymphocytes and in the splenocytes from ovalbumin-sensitized mice. Furthermore, we show that C19 can inhibit CCL11-induced chemotaxis of mouse eosinophils and human CCR3-transfected or mouse Ccr3-transfected HEK293 cells. In vivo chemotaxis assays revealed that C19 and C27 can reduce CCL11-mediated recruitment of eosinophils into the peritoneal cavity and that this inhibitory effect is stronger for C19 than for C27.

Conclusions:

Thus, C19 can attenuate airway eosinophilia and lung inflammation by inhibiting CCR3- and CCR4-mediated chemotaxis in a mouse model of asthma. Given its ability to inhibit human CCR3- and CCR4-meditated chemotaxis, C19 has great therapeutic potential for use in the treatment and control of allergic asthma.

语种: 英语
所属项目编号: 2006AA02A305 ; 2009ZX09103-724 ; 30872292 ; 90813025 ; 30825019
项目资助者: National High-Tech Research and Development Program of China ; National Key New Drug Creation Program of China ; National Natural Science Foundation of China
WOS记录号: WOS:000285923500018
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51698
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Med Immunol, Beijing 100191, Peoples R China
2.Peking Univ, Human Dis Genom Ctr, Beijing 100191, Peoples R China
3.Zhejiang Univ, Affiliated Hosp 2, Dept Resp Med, Inst Resp Dis,Sch Med, Hangzhou, Zhejiang, Peoples R China
4.Hangzhou First Peoples Hosp, Work Dept Resp Med, Hangzhou, Zhejiang, Peoples R China

Recommended Citation:
Tian, L.,Li, W.,Wang, J.,et al. The CKLF1-C19 peptide attenuates allergic lung inflammation by inhibiting CCR3- and CCR4-mediated chemotaxis in a mouse model of asthma[J]. ALLERGY,2011,66(2):287-297.
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