MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation
Autor(a) principal: | |
---|---|
Data de Publicação: | 2015 |
Outros Autores: | , , , , , |
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. |
id |
UNSP_fe830a6c0a11ae497ae449f7ec705dcf |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/129369 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
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 |
dc.relation.none.fl_str_mv |
Plos One 2.766 1,164 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1-13 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 |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129419791826944 |