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学科主题: 临床医学
题名:
Flagellin Induces the Expression of Thymic Stromal Lymphopoietin in Human Keratinocytes via Toll-Like Receptor 5
作者: Tuan Anh Le2,3; Takai, Toshiro1; Anh Tuan Vu2,4; Kinoshita, Hirokazu2; Chen, Xue5; Ikeda, Shigaku2; Ogawa, Hideoki; Okumura, Ko
关键词: Thymic stromal lymphopoietin ; Keratinocyte ; Flagellin ; Toll-like receptor 5 ; Cytokine milieu ; Atopic dermatitis ; T helper 2 ; Epidermal growth factor receptor ligand
刊名: INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
发表日期: 2011
DOI: 10.1159/000318679
卷: 155, 期:1, 页:31-37
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]: INNATE IMMUNE-RESPONSE ; EPIDERMAL BARRIER DYSFUNCTION ; HUMAN EPITHELIAL-CELLS ; ATOPIC-DERMATITIS ; T-CELLS ; ALLERGIC INFLAMMATION ; TLR EXPRESSION ; TH2 CYTOKINES ; CUTTING EDGE ; GLUCOCORTICOIDS
英文摘要:

Background: Thymic stromal lymphopoietin (TSLP), highly expressed by keratinocytes in skin lesions of atopic dermatitis patients and bronchial epithelial cells in asthma, plays a key role in allergic diseases. Information on triggers for the release of TSLP in keratinocytes is still limited. Keratinocytes express Toll-like receptor (TLR) 5, the ligand for which is flagellin, the major structural protein of the flagella of Gram-negative bacteria. IL-4, IL-13 and TNF-alpha (Th2/TNF) are associated with allergic diseases. TGF-alpha, one of the ligands for the epidermal growth factor receptor, is overexpressed in keratinocytes in atopic dermatitis. We investigated the induction of TSLP expression in keratinocytes stimulated with flagellin and its modulation by the Th2/TNF cytokines and TGF-alpha. Methods: Primary human keratinocytes were stimulated with flagellin with or without cytokines. The TSLP released was measured by ELISA. Gene expression was analyzed by quantitative real-time PCR. Results: Stimulation of keratinocytes with flagellin induced the release of TSLP protein and upregulation of the gene expression of TSLP and other pro-inflammatory molecules. The flagellin-induced release of TSLP was enhanced by the Th2/TNF cytokines or TGF-alpha. Small interfering RNA-mediated knockdown of TLR5 expression suppressed the flagellin-induced TSLP gene expression. Conclusions: Flagellin induces TSLP expression in keratinocytes via TLR5 and the expression can be upregulated by a cytokine milieu with Th2/TNF or TGF-alpha, suggesting that exposure of barrier-defective skin to Gram-negative bacteria or environmental flagellin contributes to the initiation and/or amplification of Th2-type skin inflammation including atopic dermatitis through the induction of TSLP expression in keratinocytes. Copyright (C) 2010 S. Karger AG, Basel

语种: 英语
WOS记录号: WOS:000289891700004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55048
Appears in Collections:北京大学第二临床医学院_皮科_期刊论文

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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.Inst Clin Med & Pharmaceut Sci 108, Dept Dermatol & Allergol, Hanoi, Vietnam
5.Peking Univ, Peoples Hosp, Dept Dermatol, Beijing 100871, Peoples R China

Recommended Citation:
Tuan Anh Le,Takai, Toshiro,Anh Tuan Vu,et al. Flagellin Induces the Expression of Thymic Stromal Lymphopoietin in Human Keratinocytes via Toll-Like Receptor 5[J]. INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY,2011,155(1):31-37.
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