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

Cell Rep. 2018 Feb 13;22(7):1810-1823. doi: 10.1016/j.celrep.2018.01.058.


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.

Keywords: NF-κB; epithelium; inflammation; miR-223; microRNA; neutrophils; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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


  • MIRN223 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Zebrafish Proteins
  • microRNA-223, zebrafish