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

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

Author information

1
Organ Protection Program, Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045, USA. viola.neudecker@med.uni-muenchen.de.
2
Department of Anesthesiology, University Hospital, Ludwig-Maximilian University of Munich, 81377 Munich, Germany.
3
Organ Protection Program, Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045, USA.
4
Program in Translational Lung Research, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
5
Department of Immunology and Microbiology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, CO 80206, USA.
6
Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
7
Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
8
Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
9
Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
10
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics, Digestive Health Institute, Children's Hospital Colorado; Mucosal Inflammation Program, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
11
Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
12
Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
13
Department of Neurosurgery, University of Colorado Denver, Aurora, CO 80045, USA.
14
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany.
15
Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

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.

PMID:
28931657
PMCID:
PMC5842431
DOI:
10.1126/scitranslmed.aah5360
[Indexed for MEDLINE]
Free PMC Article

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