MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation

Detalhes bibliográficos
Autor(a) principal: Wang, Zhuo
Data de Publicação: 2015
Outros Autores: Brandt, Stephanie, Medeiros, Alexandra [UNESP], Wang, Soujuan, Wu, Hao, Dent, Alexander, Serezani, C. Henrique
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115855
http://hdl.handle.net/11449/129369
Resumo: Macrophages 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 E-2 (PGE(2)) is a determining factor in macrophage polarization. miR-21 inhibition impairs expression of M2 signature genes but not M1 genes. PGE(2) 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 PGE(2)-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.
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spelling MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generationMacrophages 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 E-2 (PGE(2)) is a determining factor in macrophage polarization. miR-21 inhibition impairs expression of M2 signature genes but not M1 genes. PGE(2) 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 PGE(2)-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.National Institutes of HealthRalph W. and Grace M. Showalter Research Trust FundFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Indiana Univ Sch Med, Dept Microbiol &Immunol, Indianapolis, IN 46202 USAUniv Estadual Paulista, Fac Ciencias Farmaceut, Dept Ciencias Biol, BR-14801902 Araraquara, SP, BrazilUniv Estadual Paulista, Fac Ciencias Farmaceut, Dept Ciencias Biol, BR-14801902 Araraquara, SP, BrazilNational Institutes of Health: 1R21AI079349-01National Institutes of Health: HL-103777-01National Institutes of Health: HL-124159-01National Institutes of Health: T32AI060519Public Library ScienceIndiana Univ Sch MedUniversidade Estadual Paulista (Unesp)Wang, ZhuoBrandt, StephanieMedeiros, Alexandra [UNESP]Wang, SoujuanWu, HaoDent, AlexanderSerezani, C. Henrique2015-10-21T20:56:44Z2015-10-21T20:56:44Z2015-02-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1-13application/pdfhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115855Plos One. San Francisco: Public Library Science, v. 10, n. 2, p. 1-13, 2015.1932-6203http://hdl.handle.net/11449/12936910.1371/journal.pone.0115855WOS:000350662100020WOS000350662100020.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPlos One2.7661,164info:eu-repo/semantics/openAccess2024-06-24T13:08:24Zoai:repositorio.unesp.br:11449/129369Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:21:33.066297Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation
title MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation
spellingShingle MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation
Wang, Zhuo
title_short MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation
title_full MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation
title_fullStr MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation
title_full_unstemmed MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation
title_sort MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation
author Wang, Zhuo
author_facet Wang, Zhuo
Brandt, Stephanie
Medeiros, Alexandra [UNESP]
Wang, Soujuan
Wu, Hao
Dent, Alexander
Serezani, C. Henrique
author_role author
author2 Brandt, Stephanie
Medeiros, Alexandra [UNESP]
Wang, Soujuan
Wu, Hao
Dent, Alexander
Serezani, C. Henrique
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Indiana Univ Sch Med
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Wang, Zhuo
Brandt, Stephanie
Medeiros, Alexandra [UNESP]
Wang, Soujuan
Wu, Hao
Dent, Alexander
Serezani, C. Henrique
description Macrophages 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 E-2 (PGE(2)) is a determining factor in macrophage polarization. miR-21 inhibition impairs expression of M2 signature genes but not M1 genes. PGE(2) 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 PGE(2)-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.
publishDate 2015
dc.date.none.fl_str_mv 2015-10-21T20:56:44Z
2015-10-21T20:56:44Z
2015-02-23
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115855
Plos One. San Francisco: Public Library Science, v. 10, n. 2, p. 1-13, 2015.
1932-6203
http://hdl.handle.net/11449/129369
10.1371/journal.pone.0115855
WOS:000350662100020
WOS000350662100020.pdf
url http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115855
http://hdl.handle.net/11449/129369
identifier_str_mv Plos One. San Francisco: Public Library Science, v. 10, n. 2, p. 1-13, 2015.
1932-6203
10.1371/journal.pone.0115855
WOS:000350662100020
WOS000350662100020.pdf
dc.language.iso.fl_str_mv eng
language eng
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application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
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reponame_str Repositório Institucional da UNESP
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repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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