Peer-Reviewed Journal Details
Mandatory Fields
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
September
Science Translational Medicine
Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice
Published
1 ()
Optional Fields
RESPIRATORY-DISTRESS-SYNDROME ALVEOLAR TYPE-II POLY(ADP-RIBOSE) POLYMERASE-1 INTERCELLULAR COMMUNICATION MEDIATED ENDOCYTOSIS ADENOSINE MICRORNA-223 INFLAMMATION MECHANISM MICROPARTICLES
9
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
WASHINGTON
1946-6234
10.1126/scitranslmed.aah5360
Grant Details