Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice.
Sci Transl Med
; 9(408)2017 Sep 20.
Article
em En
| MEDLINE
| ID: mdl-28931657
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Células Epiteliais
/
Lesão Pulmonar Aguda
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Pulmão
/
Neutrófilos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Sci Transl Med
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos