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dc.contributor.authorFredman, Gabrielle
dc.contributor.authorLi, Yongsheng
dc.contributor.authorDalli, Jesmond P
dc.contributor.authorChiang, Nan
dc.contributor.authorSerhan, Charles Nicholas
dc.date.accessioned2013-04-15T16:52:05Z
dc.date.issued2012
dc.identifier.citationFredman, Gabrielle, Yongsheng Li, Jesmond Dalli, Nan Chiang, and Charles N. Serhan. 2012. Self-limited versus delayed resolution of acute inflammation: temporal regulation of pro-resolving mediators and microRNA. Scientific Reports 2:639.en_US
dc.identifier.issn2045-2322en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10533605
dc.description.abstractMechanisms underlying delays in resolution programs of inflammation are of interest for many diseases. Here, we addressed delayed resolution of inflammation and identified specific microRNA (miR)-metabolipidomic signatures. Delayed resolution initiated by high-dose challenges decreased miR-219-5p expression along with increased leukotriene B4 (5-fold) and decreased (~3-fold) specialized pro-resolving mediators, e.g. protectin D1. Resolvin (Rv)E1 and RvD1 (1 nM) reduced miR-219-5p in human macrophages, not shared by RvD2 or PD1. Since mature miR-219-5p is produced from pre-miRs miR-219-1 and miR-219-2, we co-expressed in human macrophages a 5-lipoxygenase (LOX) 3′UTR-luciferase reporter vector together with either miR-219-1 or miR-219-2. Only miR-219-2 reduced luciferase activity. Apoptotic neutrophils administered into inflamed exudates in vivo increased miR-219-2-3p expression and PD1/NPD1 levels as well as decreased leukotriene B4. These results demonstrate that delayed resolution undermines endogenous resolution programs, altering miR-219-2 expression, increasing pro-inflammatory mediators and compromising SPM production that contribute to failed catabasis and homeostasis.en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/srep00639en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434392/pdf/en_US
dash.licenseLAA
dc.titleSelf-Limited versus Delayed Resolution of Acute Inflammation: Temporal Regulation of Pro-Resolving Mediators and MicroRNAen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalScientific Reportsen_US
dash.depositing.authorChiang, Nan
dc.date.available2013-04-15T16:52:05Z
dc.identifier.doi10.1038/srep00639*
dash.contributor.affiliatedLi, Yongsheng
dash.contributor.affiliatedFredman, Gabrielle
dash.contributor.affiliatedChiang, Nan
dash.contributor.affiliatedDalli, Jesmond P
dash.contributor.affiliatedSerhan, Charles


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