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タイトル: | In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines. |
著者: | Mizuno, Rei ![]() Kamioka, Yuji Kabashima, Kenji ![]() ![]() ![]() Imajo, Masamichi ![]() Sumiyama, Kenta Nakasho, Eiji Ito, Takeshi ![]() ![]() Hamazaki, Yoko ![]() ![]() Okuchi, Yoshihisa Sakai, Yoshiharu Kiyokawa, Etsuko Matsuda, Michiyuki ![]() ![]() ![]() |
著者名の別形: | 水野, 礼 松田, 道行 |
発行日: | 19-May-2014 |
出版者: | Rockefeller University Press |
誌名: | The Journal of experimental medicine |
巻: | 211 |
号: | 6 |
開始ページ: | 1123 |
終了ページ: | 1136 |
抄録: | Many chemical mediators regulate neutrophil recruitment to inflammatory sites. Although the actions of each chemical mediator have been demonstrated with neutrophils in vitro, how such chemical mediators act cooperatively or counteractively in vivo remains largely unknown. Here, by in vivo two-photon excitation microscopy with transgenic mice expressing biosensors based on Förster resonance energy transfer, we time-lapse-imaged the activities of extracellular signal-regulated kinase (ERK) and protein kinase A (PKA) in neutrophils in inflamed intestinal tissue. ERK activity in neutrophils rapidly increased during spreading on the endothelial cells and showed positive correlation with the migration velocity on endothelial cells or in interstitial tissue. Meanwhile, in the neutrophils migrating in the interstitial tissue, high PKA activity correlated negatively with migration velocity. In contradiction to previous in vitro studies that showed ERK activation by prostaglandin E2 (PGE2) engagement with prostaglandin receptor EP4, intravenous administration of EP4 agonist activated PKA, inhibited ERK, and suppressed migration of neutrophils. The opposite results were obtained using nonsteroidal antiinflammatory drugs (NSAIDs). Therefore, NSAID-induced enteritis may be caused at least partially by the inhibition of EP4 receptor signaling of neutrophils. Our results demonstrate that ERK positively regulates the neutrophil recruitment cascade by promoting adhesion and migration steps. |
記述: | 生きたマウスの白血球の中で分子活性を可視化することに世界で初めて成功 -非ステロイド性抗炎症薬は白血球を活性化する-. 京都大学プレスリリース. 2014-05-26. |
著作権等: | © 2014 Mizuno et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
URI: | http://hdl.handle.net/2433/187372 |
DOI(出版社版): | 10.1084/jem.20132112 |
PubMed ID: | 24842369 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2014-05-26 |
出現コレクション: | 学術雑誌掲載論文等 |
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