Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice

Sci Transl Med. 2017 Sep 20;9(408):eaah5360. doi: 10.1126/scitranslmed.aah5360.

Abstract

Intercellular transfer of microRNAs can mediate communication between critical effector cells. We hypothesized that transfer of neutrophil-derived microRNAs to pulmonary epithelial cells could alter mucosal gene expression during acute lung injury. Pulmonary-epithelial microRNA profiling during coculture of alveolar epithelial cells with polymorphonuclear neutrophils (PMNs) revealed a selective increase in lung epithelial cell expression of microRNA-223 (miR-223). Analysis of PMN-derived supernatants showed activation-dependent release of miR-223 and subsequent transfer to alveolar epithelial cells during coculture in vitro or after ventilator-induced acute lung injury in mice. Genetic studies indicated that miR-223 deficiency was associated with severe lung inflammation, whereas pulmonary overexpression of miR-223 in mice resulted in protection during acute lung injury induced by mechanical ventilation or by infection with Staphylococcus aureus Studies of putative miR-223 gene targets implicated repression of poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) in the miR-223-dependent attenuation of lung inflammation. Together, these findings suggest that intercellular transfer of miR-223 from neutrophils to pulmonary epithelial cells may dampen acute lung injury through repression of PARP-1.

MeSH terms

  • Acute Lung Injury / genetics*
  • Acute Lung Injury / pathology*
  • Animals
  • Cell Communication
  • Epithelial Cells / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Lung / pathology*
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nanoparticles / chemistry
  • Neutrophils / metabolism*
  • Pneumonia / genetics
  • Pneumonia / pathology
  • Poly(ADP-ribose) Polymerases / metabolism
  • RNA Transport

Substances

  • MIRN223 microRNA, mouse
  • MicroRNAs
  • Poly(ADP-ribose) Polymerases