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
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • HEK293 Cells
  • Neutrophils/metabolism
  • Neutrophils/pathology*
  • Zebrafish Proteins/metabolism
  • Base Sequence
  • Inflammation/metabolism
  • Inflammation/pathology*
  • Keratinocytes/metabolism*
  • Animal Fins/physiology
  • Bronchi/cytology
  • Regeneration
  • Phagocytes/metabolism
  • Embryo, Nonmammalian/metabolism
  • NF-kappa B/metabolism*
  • Epithelial Cells/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Humans
  • Animals
  • Signal Transduction*
(all 22)
PubMed
29444433 Full text @ Cell Rep.
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
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
nc1TgTransgenic Insertion
    nz117TgTransgenic Insertion
      pu8TgTransgenic Insertion
        pu9TgTransgenic Insertion
          pu10TgTransgenic Insertion
            pu11TgTransgenic Insertion
              pu12TgTransgenic Insertion
                pu13TgTransgenic Insertion
                  pu18
                    Indel
                    uwm4TgTransgenic Insertion
                      1 - 10 of 11
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Fish
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab7-tp63polyclonal
                        IgGRabbit
                        1 - 1 of 1
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                        Orthology
                        No data available
                        Engineered Foreign Genes
                        Marker Marker Type Name
                        CFPEFGCFP
                        Dendra2EFGDendra2
                        EGFPEFGEGFP
                        GAL4EFGGAL4
                        GFPEFGGFP
                        mCherryEFGmCherry
                        RFPEFGRFP
                        1 - 7 of 7
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                        Mapping
                        No data available