1. Academic Validation
  2. Ly6G+ neutrophil-derived miR-223 inhibits the NLRP3 inflammasome in mitochondrial DAMP-induced acute lung injury

Ly6G+ neutrophil-derived miR-223 inhibits the NLRP3 inflammasome in mitochondrial DAMP-induced acute lung injury

  • Cell Death Dis. 2017 Nov 16;8(11):e3170. doi: 10.1038/cddis.2017.549.
Zunyong Feng 1 2 Shimei Qi 1 3 Yue Zhang 2 Zhilin Qi 1 3 Liang Yan 1 3 Jing Zhou 1 Fang He 2 Qianqian Li 2 Yanyan Yang 2 Qun Chen 4 Shi Xiao 4 Qiang Li 1 3 Yang Chen 2 Yao Zhang 1 3
Affiliations

Affiliations

  • 1 Anhui Province Key Laboratory of Active Biological Macro-molecules, Wannan Medical College, Wuhu, China.
  • 2 Department of Forensic Medicine, Wannan Medical College, Wuhu, China.
  • 3 Department of Biochemistry, Wannan Medical College, Wuhu, China.
  • 4 Department of Intensive Care Unit, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, China.
Abstract

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-1β release; therefore, miR-223 deficiency can lead to the sustained activation of NLRP3-IL-1β. Finally, elimination of peripheral Ly6G+ neutrophils and pharmacological blockade of the miR-223-NLRP3-IL-1β 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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