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In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines
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-photo...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042632/ https://www.ncbi.nlm.nih.gov/pubmed/24842369 http://dx.doi.org/10.1084/jem.20132112 |
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author | Mizuno, Rei Kamioka, Yuji Kabashima, Kenji Imajo, Masamichi Sumiyama, Kenta Nakasho, Eiji Ito, Takeshi Hamazaki, Yoko Okuchi, Yoshihisa Sakai, Yoshiharu Kiyokawa, Etsuko Matsuda, Michiyuki |
author_facet | Mizuno, Rei Kamioka, Yuji Kabashima, Kenji Imajo, Masamichi Sumiyama, Kenta Nakasho, Eiji Ito, Takeshi Hamazaki, Yoko Okuchi, Yoshihisa Sakai, Yoshiharu Kiyokawa, Etsuko Matsuda, Michiyuki |
author_sort | Mizuno, Rei |
collection | PubMed |
description | 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 E(2) (PGE(2)) 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. |
format | Online Article Text |
id | pubmed-4042632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40426322014-12-02 In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines Mizuno, Rei Kamioka, Yuji Kabashima, Kenji Imajo, Masamichi Sumiyama, Kenta Nakasho, Eiji Ito, Takeshi Hamazaki, Yoko Okuchi, Yoshihisa Sakai, Yoshiharu Kiyokawa, Etsuko Matsuda, Michiyuki J Exp Med Article 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 E(2) (PGE(2)) 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. The Rockefeller University Press 2014-06-02 /pmc/articles/PMC4042632/ /pubmed/24842369 http://dx.doi.org/10.1084/jem.20132112 Text en © 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/). |
spellingShingle | Article Mizuno, Rei Kamioka, Yuji Kabashima, Kenji Imajo, Masamichi Sumiyama, Kenta Nakasho, Eiji Ito, Takeshi Hamazaki, Yoko Okuchi, Yoshihisa Sakai, Yoshiharu Kiyokawa, Etsuko Matsuda, Michiyuki In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines |
title | In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines |
title_full | In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines |
title_fullStr | In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines |
title_full_unstemmed | In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines |
title_short | In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines |
title_sort | in vivo imaging reveals pka regulation of erk activity during neutrophil recruitment to inflamed intestines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042632/ https://www.ncbi.nlm.nih.gov/pubmed/24842369 http://dx.doi.org/10.1084/jem.20132112 |
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