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Staphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2-Toll-like receptor 6 pathway
Vu, Anh Tuan2,4; Baba, Tadashi3; Chen, Xue5; Le, Tuan Anh2,6; Kinoshita, Hirokazu2; Xie, Yang; Kamijo, Seiji; Hiramatsu, Keiichi3; Ikeda, Shigaku2; Ogawa, Hideoki; Okumura, Ko; Takai, Toshiro1
关键词Thymic stromal lymphopoietin keratinocyte diacylated lipopeptide Staphylococcus aureus Toll-like receptor 2 Toll-like receptor 6 cytokine milieu atopic dermatitis vicious cycle
刊名JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
2010-11-01
DOI10.1016/j.jaci.2010.09.002
126期:5页:985-U145
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Allergy ; Immunology
资助者Ministry of Education, Culture, Sports, Science and Technology, Japan ; Ministry of Education, Culture, Sports, Science and Technology, Japan
研究领域[WOS]Allergy ; Immunology
关键词[WOS]SEVERE ATOPIC-DERMATITIS ; HUMAN EPITHELIAL-CELLS ; T-CELLS ; ALLERGIC INFLAMMATION ; R753Q POLYMORPHISM ; CUTTING EDGE ; SKIN ; EXPRESSION ; GLUCOCORTICOIDS ; LIPOPROTEINS
英文摘要

Background: Staphylococcus aureus heavily colonizes the lesions of patients with atopic dermatitis (AD) and is known to trigger a worsening of AD. However, the exact mechanism by which S aureus promotes AD is unknown. Thymic stromal lymphopoietin (TSLP), which is highly expressed by keratinocytes in skin lesions of patients with AD and bronchial epithelial cells in asthmatic patients, represents a critical factor linking responses at interfaces between the body and the environment to allergic type 2 immune responses.

Objectives: We sought to examine the ability of synthetic lipopeptides and S aureus to induce TSLP expression in human keratinocytes and identify the pathway of induction. Methods: We stimulated primary human keratinocytes with lipopeptides and S aureus-derived materials. The release and gene expression of TSLP were measured by means of ELISA and quantitative PCR, respectively.

Results: Diacylated lipopeptide upregulated the expression of TSLP and other proinflammatory molecules. Heat-killed S aureus and the subcellular fractions of S aureus induced TSLP′s release, with the membranous fraction having the greatest activity. Small interfering RNA-mediated knockdown of either Toll-like receptor (TLR) 2 or TLR6 inhibited the diacylated lipopeptide- and S aureus membrane-induced TSLP gene expression. S aureus membrane- and diacylated lipopeptide-induced release of TSLP was enhanced by T(H)2/TNF-alpha cytokines and partially suppressed by IFN-gamma and TGF-beta.

Conclusions: The results suggest that ligands for the TLR2-TLR6 heterodimer in S aureus membranes, including diacylated lipoproteins, could promote T(H)2-type inflammation through TSLP production in keratinocytes, providing an overall picture of the vicious cycles between colonization by S aureus and AD in the T(H)2-skewed sensitization process, exacerbation of the disease, or both. (J Allergy Clin Immunol 2010;126:985-93.)

语种英语
资助者Ministry of Education, Culture, Sports, Science and Technology, Japan ; Ministry of Education, Culture, Sports, Science and Technology, Japan
WOS记录号WOS:000283727100014
引用统计
被引频次:61[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/400002259/60164
专题北京大学第二临床医学院_皮科
作者单位1.Quyhoa Natl Leprosy Dermatol Hosp, Quynhon, Vietnam
2.Juntendo Univ, Grad Sch Med, Atopy Allergy Res Ctr, Bunkyo Ku, Tokyo 1138421, Japan
3.Juntendo Univ, Grad Sch Med, Dept Dermatol & Allergol, Tokyo 1138421, Japan
4.Juntendo Univ, Grad Sch Med, Dept Microbiol & Infect Control Sci, Tokyo 1138421, Japan
5.Peking Univ, Peoples Hosp, Dept Dermatol, Beijing 100871, Peoples R China
6.Inst Clin Med & Pharmaceut Sci 108, Dept Dermatol & Allergol, Hanoi, Vietnam
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Vu, Anh Tuan,Baba, Tadashi,Chen, Xue,et al. Staphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2-Toll-like receptor 6 pathway[J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,2010,126(5):985-U145.
APA Vu, Anh Tuan.,Baba, Tadashi.,Chen, Xue.,Le, Tuan Anh.,Kinoshita, Hirokazu.,...&Takai, Toshiro.(2010).Staphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2-Toll-like receptor 6 pathway.JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,126(5),985-U145.
MLA Vu, Anh Tuan,et al."Staphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2-Toll-like receptor 6 pathway".JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 126.5(2010):985-U145.
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