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

Neudecker, Viola; Brodsky, Kelley S.; Clambey, Eric T.; Schmidt, Eric P.; Packard, Thomas A.; Davenport, Bennett; Standiford, Theodore J.; Weng, Tingting; Fletcher, Ashley A.; Barthel, Lea; Masterson, Joanne C.; Furuta, Glenn T.; Cai, Chunyan; Blackburn, Michael R.; Ginde, Adit A.; Graner, Michael W.; Janssen, William J.; Zemans, Rachel L.; Evans, Christopher M.; Burnham, Ellen L.; Homann, Dirk; Moss, Marc; Kreth, Simone; Zacharowski, Kai; Henson, Peter M.; Eltzschig, Holger K. (2017): Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice. In: Science Translational Medicine, Vol. 9, No. 408, eaah5360

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 (miR223). 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 associatedwith 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 diphosphateribose) 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

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1946-6234
• Language: English