ZFIN ID: ZDB-PUB-180223-12
MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation
Zhou, W., Pal, A.S., Hsu, A.Y., Gurol, T., Zhu, X., Wirbisky-Hershberger, S.E., Freeman, J.L., Kasinski, A.L., Deng, Q.
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
Microarrays: GEO:GSE94996
MeSH Terms:
  • Animal Fins/physiology
  • Animals
  • Base Sequence
  • Bronchi/cytology
  • Embryo, Nonmammalian/metabolism
  • Epithelial Cells/metabolism
  • HEK293 Cells
  • Humans
  • Inflammation/metabolism
  • Inflammation/pathology*
  • Keratinocytes/metabolism*
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • NF-kappa B/metabolism*
  • Neutrophils/metabolism
  • Neutrophils/pathology*
  • Phagocytes/metabolism
  • Regeneration
  • Signal Transduction*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/metabolism
PubMed: 29444433 Full text @ Cell Rep.
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.