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MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation

MicroRNA-223 is known as a myeloid-enriched anti-inflammatory microRNA that is dysregulated in numerous inflammatory conditions. Here, we report that neutrophilic inflammation (wound response) is augmented in miR-223-deficient zebrafish, due primarily to elevated activation of the canonical nuclear...

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Autores principales: Zhou, Wenqing, Pal, Arpita S., Hsu, Alan Yi-Hui, Gurol, Theodore, Zhu, Xiaoguang, Wirbisky-Hershberger, Sara E., Freeman, Jennifer L., Kasinski, Andrea L., Deng, Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839657/
https://www.ncbi.nlm.nih.gov/pubmed/29444433
http://dx.doi.org/10.1016/j.celrep.2018.01.058
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author Zhou, Wenqing
Pal, Arpita S.
Hsu, Alan Yi-Hui
Gurol, Theodore
Zhu, Xiaoguang
Wirbisky-Hershberger, Sara E.
Freeman, Jennifer L.
Kasinski, Andrea L.
Deng, Qing
author_facet Zhou, Wenqing
Pal, Arpita S.
Hsu, Alan Yi-Hui
Gurol, Theodore
Zhu, Xiaoguang
Wirbisky-Hershberger, Sara E.
Freeman, Jennifer L.
Kasinski, Andrea L.
Deng, Qing
author_sort Zhou, Wenqing
collection PubMed
description MicroRNA-223 is known as a myeloid-enriched anti-inflammatory microRNA that is dysregulated in numerous inflammatory conditions. Here, we report that neutrophilic inflammation (wound response) is augmented in miR-223-deficient zebrafish, due primarily to elevated activation of the canonical nuclear factor κB (NF-κB) pathway. NF-κB over-activation is restricted to the basal layer of the surface epithelium, although miR-223 is detected throughout the epithelium and in phagocytes. Not only phagocytes but also epithelial cells are involved in miR-223-mediated regulation of neutrophils’ wound response and NF-κB activation. Cul1a/b, Traf6, and Tab1 are identified as direct targets of miR-223, and their levels rise in injured epithelium lacking miR-223. In addition, miR-223 is expressed in cultured human bronchial epithelial cells, where it also downregulates NF-κB signaling. Together, this direct connection between miR-223 and the canonical NF-κB pathway provides a mechanistic understanding of the multifaceted role of miR-223 and highlights the relevance of epithelial cells in dampening neutrophil activation.
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spelling pubmed-58396572018-03-06 MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation Zhou, Wenqing Pal, Arpita S. Hsu, Alan Yi-Hui Gurol, Theodore Zhu, Xiaoguang Wirbisky-Hershberger, Sara E. Freeman, Jennifer L. Kasinski, Andrea L. Deng, Qing Cell Rep Article MicroRNA-223 is known as a myeloid-enriched anti-inflammatory microRNA that is dysregulated in numerous inflammatory conditions. Here, we report that neutrophilic inflammation (wound response) is augmented in miR-223-deficient zebrafish, due primarily to elevated activation of the canonical nuclear factor κB (NF-κB) pathway. NF-κB over-activation is restricted to the basal layer of the surface epithelium, although miR-223 is detected throughout the epithelium and in phagocytes. Not only phagocytes but also epithelial cells are involved in miR-223-mediated regulation of neutrophils’ wound response and NF-κB activation. Cul1a/b, Traf6, and Tab1 are identified as direct targets of miR-223, and their levels rise in injured epithelium lacking miR-223. In addition, miR-223 is expressed in cultured human bronchial epithelial cells, where it also downregulates NF-κB signaling. Together, this direct connection between miR-223 and the canonical NF-κB pathway provides a mechanistic understanding of the multifaceted role of miR-223 and highlights the relevance of epithelial cells in dampening neutrophil activation. 2018-02-13 /pmc/articles/PMC5839657/ /pubmed/29444433 http://dx.doi.org/10.1016/j.celrep.2018.01.058 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zhou, Wenqing
Pal, Arpita S.
Hsu, Alan Yi-Hui
Gurol, Theodore
Zhu, Xiaoguang
Wirbisky-Hershberger, Sara E.
Freeman, Jennifer L.
Kasinski, Andrea L.
Deng, Qing
MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation
title MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation
title_full MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation
title_fullStr MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation
title_full_unstemmed MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation
title_short MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation
title_sort microrna-223 suppresses the canonical nf-κb pathway in basal keratinocytes to dampen neutrophilic inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839657/
https://www.ncbi.nlm.nih.gov/pubmed/29444433
http://dx.doi.org/10.1016/j.celrep.2018.01.058
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