| Popis: |
MicroRNA‐223, a principally myeloid‐specific anti‐inflammatory microRNA, is dysregulated in numerous inflammatory conditions. Here we report that miR223 deficient zebrafish displayed augmented neutrophilic inflammation, which was due primarily to elevated activation of the canonical NF‐κB pathway. Cul1a/b, Traf6 and Tab1 were identified as direct targets of miR‐223. Unexpectedly, the NF‐κB over‐activation was restricted to the basal epithelial cells, a squamous layer between the basal membrane and the apical epithelium. MiR‐223 was detected in both apical and basal epithelium besides phagocytes. Not only phagocytes, but also epithelial cells were involved in miR‐223 mediated regulation of neutrophil wound response and NF‐κB activation. In addition, miR‐223 was expressed in human bronchial epithelial cells and directly down‐regulated NF‐κB signaling components in human. Together, our data demonstrated a direct connection of miR‐223 and the canonical NF‐κB pathway, providing a mechanistically understanding of the multifaceted role of miR‐223 and highlighted the previously overlooked relevance of epithelial cells. |
