Journal
CELL DEATH & DISEASE
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2017.549
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Funding
- National Natural Science Foundation of China [31301171, 81601380]
- Natural Science Foundation of Anhui Province, China [KJ2016SD59]
- Outstanding Young Talent Support Program Key Projects in Anhui Colleges and Universities [gxyqZD2016173]
- Natural Science Research Project in colleges and universities of Anhui Province [KJ2016A734, KJ2017A256]
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MicroRNA (miRNA) mediates RNA interference to regulate a variety of innate immune processes, but how miRNAs coordinate the mechanisms underlying acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with pulmonary inflammatory injury is still unknown. In this study, we demonstrated that miR-223 limits the number of Ly6G+ neutrophils and inhibits the activity of the NLRP3 inflammasome to alleviate ALI induced by mitochondrial damage-associated molecular patterns (DAMPs) (MTDs). miR-223 expression is increased in the lungs of MTD-induced mice or ARDS patients following trauma/transfusion or following the physiological remission of ALI/ARDS. miR-223-/+ mice exhibited more severe ALI and cytokine dysregulation. Other studies have shown that MTD-induced increases in miR-223 expression are mainly contributed by Ly6G+ neutrophils from the haematopoietic system. miR-223 blocks bone marrow-derived Ly6G+ neutrophil differentiation and inhibits peripheral cytokine release. In addition, MTD-induced miR-223 expression activates a negative feedback pathway that targets the inhibition of NLRP3 expression and IL-1 beta release; therefore, miR-223 deficiency can lead to the sustained activation of NLRP3IL-1 beta. Finally, elimination of peripheral Ly6G+ neutrophils and pharmacological blockade of the miR-223-NLRP3-IL-1 beta signalling axis could alleviate MTD-induced ALI. In summary, miR-223 is essential for regulating the pathogenesis of DAMP-induced ALI.
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