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学科主题临床医学
Fenoterol, a beta(2)-adrenoceptor agonist, inhibits LPS-induced membrane-bound CD14, TLR4/CD14 complex, and inflammatory cytokines production through beta-arrestin-2 in THP-1 cell line
Wang, Wei1; Xu, Ming2,3; Zhang, You-yi2,3; He, Bei1
关键词beta(2)-adrenoceptor toll-like receptors beta-arrestin-2 fenoterol confocal microscopy lipopolysaccharide
刊名ACTA PHARMACOLOGICA SINICA
2009-11-01
DOI10.1038/aps.2009.153
30期:11页:1522-1528
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]BETA-2-ADRENERGIC RECEPTOR ; MAPK ACTIVATION ; P38 MAPK ; ENDOCYTOSIS ; CHEMOTAXIS ; PROPIONATE ; SALMETEROL ; IMMUNITY ; INNATE
英文摘要

Aim: To investigate the molecular mechanism and signaling pathway by which fenoterol, a beta(2)-adrenergic receptor (beta(2)-AR) agonist, produces anti-inflammatory effects.

Methods: THP-1, a monocytic cell line, was used to explore the mechanism of beta(2)-AR stimulation in LPS-induced secretion of inflammatory cytokines and changes of toll-like receptors (TLRs). We labeled TLR4 and CD14 using monoclonal anti-TLR4 PE-conjugated and anti-CD14 FITC-conjugated antibodies in THP-1 cells stimulated by beta(2)-AR in the presence or absence of lipopolysaccharide (LPS) and small, interfering RNA (siRNA)-mediated knockdown of beta-arrestin-2, and then analyzed their changes in distribution by flow cytometry, Western blotting and confocal analysis.

Results: LPS-induced membrane-bound CD14, TLR4/CD14 complex levels and elevation of inflammatory cytokines were all significantly reduced by pre-incubation of fenoterol (P<0.05). However, the total level of CD14 and TLR4 was not significantly changed. Interestingly, confocal microscopy revealed redistribution of CD14 and TLR4/CD14 complex under beta(2)-AR stimulation. Furthermore, siRNA-mediated knockdown of beta-arrestin-2 eliminated the anti-inflammatory effects and redistribution of CD14 and TLR4/CD14 complex stimulated by beta(2)-AR.

Conclusion: beta(2)-AR agonist exerts its anti-inflammatory effects by down-regulating TLR signaling in THP-1 cells, potentially resulting from beta-arrestin-2 mediated redistribution of CD14 and TLR14/CD14 complex.

语种英语
WOS记录号WOS:000271953500006
项目编号2006CB503806 ; 30770939 ; 30821001
资助机构National Key Basic Research Program (NKBRP) of People&prime ; s Republic of China ; National Natural Science Foundation of China
引用统计
被引频次:16[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/400002259/67501
专题北京大学第三临床医学院_呼吸科
作者单位1.Peking Univ, Hosp 3, Dept Resp Med, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100191, Peoples R China
3.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Wang, Wei,Xu, Ming,Zhang, You-yi,et al. Fenoterol, a beta(2)-adrenoceptor agonist, inhibits LPS-induced membrane-bound CD14, TLR4/CD14 complex, and inflammatory cytokines production through beta-arrestin-2 in THP-1 cell line[J]. ACTA PHARMACOLOGICA SINICA,2009,30(11):1522-1528.
APA Wang, Wei,Xu, Ming,Zhang, You-yi,&He, Bei.(2009).Fenoterol, a beta(2)-adrenoceptor agonist, inhibits LPS-induced membrane-bound CD14, TLR4/CD14 complex, and inflammatory cytokines production through beta-arrestin-2 in THP-1 cell line.ACTA PHARMACOLOGICA SINICA,30(11),1522-1528.
MLA Wang, Wei,et al."Fenoterol, a beta(2)-adrenoceptor agonist, inhibits LPS-induced membrane-bound CD14, TLR4/CD14 complex, and inflammatory cytokines production through beta-arrestin-2 in THP-1 cell line".ACTA PHARMACOLOGICA SINICA 30.11(2009):1522-1528.
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