MicroRNA-223 Suppresses the Canonical NF-kB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation
| Autor: | Qing Deng, Arpita S. Pal, Andrea L. Kasinski, Xiaoguang Zhu, Theodore Gurol, Wenqing Zhou, Sara E. Wirbisky-Hershberger, Jennifer L. Freeman, Alan Y. Hsu |
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| Rok vydání: | 2018 |
| Předmět: |
Keratinocytes
0301 basic medicine Embryo Nonmammalian Bronchi Inflammation Neutrophilic inflammation Article NF-κB General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound Basal (phylogenetics) neutrophils mir-223 microRNA medicine Medicine and Health Sciences Animals Humans Regeneration lcsh:QH301-705.5 Zebrafish Biology Phagocytes Base Sequence biology NF-kappa B Epithelial Cells Zebrafish Proteins biology.organism_classification miR-223 Epithelium 3. Good health Cell biology MicroRNAs HEK293 Cells 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) chemistry inflammation Animal Fins medicine.symptom epithelium Signal Transduction |
| Zdroj: | Department of Biological Sciences Faculty Publications Cell Reports, Vol 22, Iss 7, Pp 1810-1823 (2018) Cell reports |
| Popis: | SUMMARY 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. In Brief microRNA-223 is dysregulated in many inflammatory conditions such as cancer and asthma, yet its physiological role is not clear. Zhou et al. demonstrate that microRNA-223 in both phagocytes and epithelial cells cooperate to suppress the canonical NF-κB pathway in epithelial cells to restrict the magnitude of inflammation. |
| Databáze: | OpenAIRE |
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