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 pri- marily to elevated activation of the canonical nuclear factor kB (NF-kB) pathway. NF-kB over-activation is restricted to the basal layer of the surface epithelium, although miR-223 is detected throughout the epithe- lium and in phagocytes. Not only phagocytes but also epithelial cells are involved in miR-223-medi- ated regulation of neutrophils’ wound response and NF-kB activation. Cul1a/b, Traf6, and Tab1 are iden- tified as direct targets of miR-223, and their levels rise in injured epithelium lacking miR-223. In addi- tion, miR-223 is expressed in cultured human bron- chial epithelial cells, where it also downregulates NF-kB signaling. Together, this direct connection between miR-223 and the canonical NF-kB pathway provides a mechanistic understanding of the multi- faceted role of miR-223 and highlights the relevance of epithelial cells in dampening neutrophil activation.


This is the publishers version of Zhou W, Pal AS, Hsu AY, Gurol T, Zhu X, Wirbisky-Hershberger SE, Freeman JL, Kasinski AL, Deng Q. 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.

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