| Staphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2-Toll-like receptor 6 pathway. | |
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MedLine Citation:
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PMID: 21050945 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-α cytokines and partially suppressed by IFN-γ and TGF-β. 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. |
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Authors:
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Anh Tuan Vu; Tadashi Baba; Xue Chen; Tuan Anh Le; Hirokazu Kinoshita; Yang Xie; Seiji Kamijo; Keiichi Hiramatsu; Shigaku Ikeda; Hideoki Ogawa; Ko Okumura; Toshiro Takai |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of allergy and clinical immunology Volume: 126 ISSN: 1097-6825 ISO Abbreviation: J. Allergy Clin. Immunol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-05 Completed Date: 2010-12-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 985-93, 993.e1-3 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, Bacterial
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immunology* Cell Membrane / immunology Cytokines / biosynthesis, immunology* Dermatitis, Atopic / immunology, metabolism, microbiology* Enzyme-Linked Immunosorbent Assay Gene Expression Humans Keratinocytes / immunology*, secretion Lipopeptides / immunology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / immunology Staphylococcal Infections / immunology Staphylococcus aureus / immunology Toll-Like Receptor 2 / immunology* Toll-Like Receptor 6 / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Bacterial; 0/Cytokines; 0/Lipopeptides; 0/TLR2 protein, human; 0/TLR6 protein, human; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 6; 0/thymic stromal lymphopoietin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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