| Item type |
文献 / Documents(1) |
| 公開日 |
2020-11-26 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1186/s13075-016-1035-9 |
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言語 |
ja |
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|
関連名称 |
10.1186/s13075-016-1035-9 |
| 出版タイプ |
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出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages |
|
言語 |
en |
| 著者 |
マツモト, タクヤ
タカハシ, ノブノリ
コジマ, トシヒサ
ヨシオカ, ユタカ
イシカワ, ジュン
フルカワ, コウイチ
オノ, ケンジ
サワダ, マコト
イシグロ, ナオキ
山本, 朗仁
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Background: The aim of this study was to assess the effects of soluble sialic acid-binding immunoglobulin-type lectin (sSiglec)-9 on joint inflammation and destruction in a murine collagen-induced arthritis (CIA) model and in monolayer cultures of murine macrophages (RAW264.7 cells and peritoneal macrophages) and fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis.
Methods: DBA/1J mice were immunized with type II collagen. Effects of sSiglec-9 were evaluated using a physiologic arthritis score, histological analysis, serum tumor necrosis factor (TNF)-α concentration, and the proportion of forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells. In vivo biofluorescence imaging was used to assess the distribution of sSiglec-9. Levels of M1 (TNF-α, interleukin [IL]-6, and inducible nitric oxide synthase) and M2 (CD206, Arginase-1, and IL-10) macrophage markers and phosphorylation of intracellular signaling molecules were examined in macrophages, and levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were examined in FLS.
Results: sSiglec-9 significantly suppressed the clinical and histological incidence and severity of arthritis. The proportion of Foxp3-positive Treg cells significantly improved and serum TNF-α concentration decreased in vivo. Although sSiglec-9 reduced the expression of M1 markers in macrophages, it did not affect the expression of M2 markers and MMPs in FLS. Nuclear factor (NF)-kB p65 phosphorylation was attenuated by sSiglec-9, and chemical blockade of the NF-kB pathway reduced M1 marker expression in RAW264.7 cells.
Conclusions: In this study, we have demonstrated the therapeutic effects of sSiglec-9 in a murine CIA model. The mechanism underlying these effects involves the suppression of M1 proinflammatory macrophages by inhibiting the NF-kB pathway. sSiglec-9 may provide a novel therapeutic option for patients with rheumatoid arthritis refractory to currently available drugs. |
|
言語 |
en |
| キーワード |
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|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Rheumatoid arthritis |
| キーワード |
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|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Collagen-induced arthritis |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Siglec-9 |
| 書誌情報 |
en : Arthritis Research & Therapy
巻 18,
p. 133,
発行日 2016-06-07
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
14786362 |
| 出版者 |
|
|
出版者 |
Springer Nature |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
BioMed Central |
|
言語 |
en |
| 権利情報 |
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|
言語 |
en |
|
権利情報 |
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| EID |
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|
識別子 |
321510 |
|
識別子タイプ |
URI |
| 言語 |
|
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言語 |
eng |
artreth_18_133.pdf (2.03 MB)
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