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学科主题: 临床医学
题名:
Extracellular Double-Stranded RNA Induces TSLP via an Endosomal Acidification- and NF-kappa B-Dependent Pathway in Human Keratinocytes
作者: Vu, Anh T.2,3; Chen, Xue4; Xie, Yang; Kamijo, Seiji; Ushio, Hiroko; Kawasaki, Junko2; Hara, Mutsuko; Ikeda, Shigaku2; Okumura, Ko; Ogawa, Hideoki; Takai, Toshiro1
刊名: JOURNAL OF INVESTIGATIVE DERMATOLOGY
发表日期: 2011-11-01
DOI: 10.1038/jid.2011.185
卷: 131, 期:11, 页:2205-2212
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Dermatology
研究领域[WOS]: Dermatology
关键词[WOS]: THYMIC STROMAL LYMPHOPOIETIN ; AIRWAY EPITHELIAL-CELLS ; TOLL-LIKE RECEPTOR-3 ; PROTEIN-KINASE ; T-CELLS ; ALLERGIC INFLAMMATION ; ATOPIC-DERMATITIS ; IN-VIVO ; EXPRESSION ; PKR
英文摘要:

Double-stranded RNA (dsRNA) causes keratinocytes to release thymic stromal lymphopoietin (TSLP), which plays a key role in allergic diseases. Endosomal Toll-like receptor 3 (TLR3) and cytosolic RIG-like receptors (RLRs) and PKR have been reported to recognize dsRNA. Here, we demonstrate that dsRNA induces TSLP in keratinocytes via an endosomal acidification-dependent and NF-kappa B-mediated pathway. After treatment with pharmacologic inhibitors or transfection with small interfering RNAs (siRNAs), primary human keratinocytes were stimulated. Bafilomycin A1, which inhibits endosomal acidification to block the TLR3 pathway, blocked the dsRNA-induced expression of TSLP, IL-8, IFN-beta, and other molecules including the dsRNA sensors, whereas it did not inhibit diacyllipopeptide-induced expression of TSLP and IL-8. The dsRNA-induced gene expression of TSLP depended on RelA, a component of NF-kappa B, but not IRF3, similar to IL-8 but different from IFN-beta, which depended on both IRF3 and RelA. The results indicate that endosomal acidification and the subsequent activation of NF-kappa B are necessary to sense extracellular dsRNA, suggesting the importance of the TLR3-NF-kappa B axis to trigger production of TSLP against the self dsRNA released from damaged cells or viral dsRNA, in the epidermis, relating to skin inflammation including atopic dermatitis (AD).

语种: 英语
项目资助者: Ministry of Education, Culture, Sports, Science and Technology, Japan
WOS记录号: WOS:000296240100014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60709
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.Juntendo Univ, Grad Sch Med, Atopy Allergy Res Ctr, Bunkyo Ku, Tokyo 1138421, Japan
2.Juntendo Univ, Grad Sch Med, Dept Dermatol & Allergol, Tokyo 1138421, Japan
3.Quyhoa Natl Leprosy Dermatol Hosp, Quynhon, Vietnam
4.Peking Univ, Peoples Hosp, Dept Dermatol, Beijing 100871, Peoples R China

Recommended Citation:
Vu, Anh T.,Chen, Xue,Xie, Yang,et al. Extracellular Double-Stranded RNA Induces TSLP via an Endosomal Acidification- and NF-kappa B-Dependent Pathway in Human Keratinocytes[J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY,2011,131(11):2205-2212.
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