MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E2-mediated M2 generation

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dc.contributor.authorWang, Zhuo
dc.contributor.authorBrandt, Stephanie
dc.contributor.authorMedeiros, Alexandra
dc.contributor.authorWang, Soujuan
dc.contributor.authorWu, Hao
dc.contributor.authorDent, Alexander
dc.contributor.authorSerezani, C. Henrique
dc.contributor.departmentDepartment of Microbiology and Immunology, IU School of Medicineen_US
dc.date.accessioned2016-06-16T14:04:06Z
dc.date.available2016-06-16T14:04:06Z
dc.date.issued2015-02-23
dc.description.abstractMacrophages dictate both initiation and resolution of inflammation. During acute inflammation classically activated macrophages (M1) predominate, and during the resolution phase alternative macrophages (M2) are dominant. The molecular mechanisms involved in macrophage polarization are understudied. MicroRNAs are differentially expressed in M1 and M2 macrophages that influence macrophage polarization. We identified a role of miR-21 in macrophage polarization, and found that cross-talk between miR-21 and the lipid mediator prostaglandin E2 (PGE2) is a determining factor in macrophage polarization. miR-21 inhibition impairs expression of M2 signature genes but not M1 genes. PGE2 and its downstream effectors PKA and Epac inhibit miR-21 expression and enhance expression of M2 genes, and this effect is more pronounced in miR-21-/- cells. Among potential targets involved in macrophage polarization, we found that STAT3 and SOCS1 were enhanced in miR-21-/- cells and further enhanced by PGE2. We found that STAT3 was a direct target of miR-21 in macrophages. Silencing the STAT3 gene abolished PGE2-mediated expression of M2 genes in miR-21-/- macrophages. These data shed light on the molecular brakes involved in homeostatic macrophage polarization and suggest new therapeutic strategies to prevent inflammatory responses.en_US
dc.identifier.citationWang, Z., Brandt, S., Medeiros, A., Wang, S., Wu, H., Dent, A., & Serezani, C. H. (2015). MicroRNA 21 Is a Homeostatic Regulator of Macrophage Polarization and Prevents Prostaglandin E2-Mediated M2 Generation. PLoS ONE, 10(2), e0115855. http://doi.org/10.1371/journal.pone.0115855en_US
dc.identifier.urihttps://hdl.handle.net/1805/9995
dc.language.isoen_USen_US
dc.publisherPLoSen_US
dc.relation.isversionof10.1371/journal.pone.0115855en_US
dc.relation.journalPLoS ONEen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectAcetylcysteineen_US
dc.subjectCell Polarityen_US
dc.subjectErythromycinen_US
dc.subjectHomeostasisen_US
dc.subjectMacrophage Activationen_US
dc.subjectMacrophagesen_US
dc.subjectMicroRNAsen_US
dc.subjectSTAT3 Transcription Factoren_US
dc.subjectSuppressor of Cytokine Signaling Proteinsen_US
dc.titleMicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E2-mediated M2 generationen_US
dc.typeArticleen_US
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