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


    Neudecker, Viola and Brodsky, Kelley S. and Clambey, Eric T. and Schmidt, Eric P. and Packard, Thomas A. and Davenport, Bennett and Standiford, Theodore J. and Weng, Tingting and Fletcher, Ashley A. and Barthel, Lea and Masterson, Joanne C. and Furuta, Glenn T. and Cai, Chunyan and Blackburn, Michael R. and Ginde, Adit A. and Graner, Michael W. and Janssen, William J. and Zemans, Rachel L. and Evans, Christopher M. and Burnham, Ellen L. and Homann, Dirk and Moss, Marc and Kreth, Simone and Zacharowski, Kai and Henson, Peter M. and Eltzschig, Holger K. (2017) Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice. Science Translational Medicine, 9 (408). eaah5360. ISSN 1946-6242

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    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.

    Item Type: Article
    Additional Information: This is the author manuscript version of the published article, which is available at: Neudecker, V; Brodsky, KS; Clambey, ET; Schmidt, EP; Packard, TA; Davenport, B; Standiford, TJ; Weng, TT; Fletcher, AA; Barthel, L; Masterson, JC; Furuta, GT; Cai, CY; Blackburn, MR; Ginde, AA; Graner, MW; Janssen, WJ; Zemans, RL; Evans, CM; Burnham, EL; Homann, D; Moss, M; Kreth, S; Zacharowski, K; Henson, PM; Eltzschig, HK (2017) 'Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice'. Science Translational Medicine, 9, Issue 408, eaah5360 DOI: 10.1126/scitranslmed.aah5360
    Keywords: Neutrophil transfer; miR-223; lung epithelial cells; acute lung injury; mice;
    Academic Unit: Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 11832
    Identification Number: https://doi.org/10.1126/scitranslmed.aah5360
    Depositing User: Joanne Masterson
    Date Deposited: 18 Nov 2019 17:32
    Journal or Publication Title: Science Translational Medicine
    Publisher: American Association for the Advancement of Science
    Refereed: Yes
    URI:

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