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  1. 学位論文
  2. 博士論文(医学)
  3. 本文

Synergistic proinflammatory responses by IL-17A and Toll-like receptor 3 in human airway epithelial cells

http://hdl.handle.net/10271/3141
http://hdl.handle.net/10271/3141
2e072fe7-71b9-4df2-bed5-8d2403852a2c
名前 / ファイル ライセンス アクション
DT_719ronbun.pdf 論文本文 (1.4 MB)
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Item type 学位論文 / Thesis or Dissertation(1)
公開日 2017-01-28
タイトル
タイトル Synergistic proinflammatory responses by IL-17A and Toll-like receptor 3 in human airway epithelial cells
言語 en
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_db06
資源タイプ doctoral thesis
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
その他のタイトル
その他のタイトル ヒト気道上皮細胞におけるIL-17AとToll様受容体3による相乗的な前炎症性反応
著者 Mori, Kazutaka

× Mori, Kazutaka

en Mori, Kazutaka

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書誌情報 en : PLoS ONE

巻 10, 号 9, p. e0139491, 発行日 2015-09-29
出版者
出版者 PLOS (Public Library of Science)
言語 en
権利
言語 en
権利情報 Copyright: 2015 Mori et al.
抄録
内容記述タイプ Abstract
内容記述 Viral respiratory infections activate the innate immune response in the airway epithelium through Toll-like receptors (TLRs) and induce airway inflammation, which causes acute exacerbation of asthma. Although increases in IL-17A expression were observed in the airway of severe asthma patients, the interaction between IL-17A and TLR activation in airway epithelium remains poorly understood. In this study, we demonstrated that IL-17A and polyI:C, the ligand of TLR3, synergistically induced the expression of proinflammatory cytokines and chemokines (G-CSF, IL-8, CXCL1, CXCL5, IL-1F9), but not type I interferon (IFN-α1, -β) in primary culture of normal human bronchial epithelial cells. Synergistic induction after co-stimulation with IL-17A and polyI:C was observed from 2 to 24 hours after stimulation. Treatment with cycloheximide or actinomycin D had no effect, suggesting that the synergistic induction occurred without de novo protein synthesis or mRNA stabilization. Inhibition of the TLR3, TLR/TIR-domain-containing adaptor-inducing interferon β (TRIF), NF-κB, and IRF3 pathways decreased the polyI:C- and IL-17A/polyI:C-induced G-CSF and IL-8 mRNA expression. Comparing the levels of mRNA induction between co-treatment with IL-17A/ polyI:C and treatment with polyI:C alone, blocking the of NF-κB pathway significantly attenuated the observed synergism. In western blotting analysis, activation of both NF-κB and IRF3 was observed in treatment with polyI:C and co-treatment with IL-17A/polyI:C; moreover, co-treatment with IL-17A/polyI:C augmented IκB-α phosphorylation as compared to polyI:C treatment alone. Collectively, these findings indicate that IL-17A and TLR3 activation cooperate to induce proinflammatory responses in the airway epithelium via TLR3/TRIF-mediated NF-κB/IRF3 activation, and that enhanced activation of the NF-κB pathway plays an essential role in synergistic induction after co-treatment with IL-17A and polyI:C in vitro.
言語 en
学位名
学位名 博士(医学)
学位の区分
内容記述 doctoral
学位の分野
内容記述 医学系研究科
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 13802
学位授与機関名 浜松医科大学
学位授与年月日
学位授与年月日 2016-03-14
学位授与番号
学位授与番号 甲第719号
EISSN
収録物識別子タイプ EISSN
収録物識別子 1932-6203
PubMed番号
識別子タイプ PMID
関連識別子 26418032
出版社DOI
識別子タイプ DOI
関連識別子 https://doi.org/10.1371/journal.pone.0139491
著者版フラグ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
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