MicroRNA 21 Is a homeostatic regulator of macrophage polarization and prevents prostaglandin e2 -mediated M2 generation

Zhuo Wang, Stephanie Brandt, Alexandra Medeiros, Soujuan Wang, Hao Wu, Alexander Dent, C. Henrique Serezani

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Article numbere0115855
JournalPLoS One
Volume10
Issue number2
DOIs
StatePublished - Feb 23 2015

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Macrophages
MicroRNAs
microRNA
Dinoprostone
prostaglandins
macrophages
Polarization
Genes
inflammation
genes
Inflammation
Gene Expression
Gene Silencing
gene silencing
Transcriptome
Brakes
cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

MicroRNA 21 Is a homeostatic regulator of macrophage polarization and prevents prostaglandin e2 -mediated M2 generation. / Wang, Zhuo; Brandt, Stephanie; Medeiros, Alexandra; Wang, Soujuan; Wu, Hao; Dent, Alexander; Serezani, C. Henrique.

In: PLoS One, Vol. 10, No. 2, e0115855, 23.02.2015.

Research output: Contribution to journalArticle

Wang, Zhuo ; Brandt, Stephanie ; Medeiros, Alexandra ; Wang, Soujuan ; Wu, Hao ; Dent, Alexander ; Serezani, C. Henrique. / MicroRNA 21 Is a homeostatic regulator of macrophage polarization and prevents prostaglandin e2 -mediated M2 generation. In: PLoS One. 2015 ; Vol. 10, No. 2.
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