PUBLICATION
MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation
- Authors
- Zhou, W., Pal, A.S., Hsu, A.Y., Gurol, T., Zhu, X., Wirbisky-Hershberger, S.E., Freeman, J.L., Kasinski, A.L., Deng, Q.
- ID
- ZDB-PUB-180223-12
- Date
- 2018
- Source
- Cell Reports 22: 1810-1823 (Journal)
- Registered Authors
- Deng, Qing, Freeman, Jennifer, Gurol, Theodore, Zhou, Wenqing
- Keywords
- NF-κB, epithelium, inflammation, miR-223, microRNA, neutrophils, zebrafish
- Datasets
- GEO:GSE94996
- MeSH Terms
-
- Animals
- Keratinocytes/metabolism*
- NF-kappa B/metabolism*
- Bronchi/cytology
- Zebrafish/embryology
- Zebrafish/genetics
- Humans
- HEK293 Cells
- Phagocytes/metabolism
- Embryo, Nonmammalian/metabolism
- Signal Transduction*
- Zebrafish Proteins/metabolism
- Base Sequence
- Neutrophils/metabolism
- Neutrophils/pathology*
- Epithelial Cells/metabolism
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Regeneration
- Animal Fins/physiology
- Inflammation/metabolism
- Inflammation/pathology*
- PubMed
- 29444433 Full text @ Cell Rep.
Citation
Zhou, W., Pal, A.S., Hsu, A.Y., Gurol, T., Zhu, X., Wirbisky-Hershberger, S.E., Freeman, J.L., Kasinski, A.L., Deng, Q. (2018) MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation. Cell Reports. 22:1810-1823.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping