miR-125a-5p regulates differential activation of macrophages and inflammation

J Biol Chem. 2013 Dec 6;288(49):35428-36. doi: 10.1074/jbc.M112.426866. Epub 2013 Oct 22.


Macrophage activation is a central event in immune responses. Macrophages undergoing classical activation (M1 macrophages) are proinflammatory, whereas alternatively activated macrophages (M2 macrophages) are generally anti-inflammatory. miRNAs play important regulatory roles in inflammatory response. However, the manner in which miRNAs regulate macrophage activation in response to different environmental cues has not been well defined. In this study, we found that M-BMM macrophages (M2) express greater levels of miR-125a-5p than do GM-BMM macrophages (M1). Stimulation of macrophages through TLR2 and TLR4 but not through TLR3 enhanced miR-125a-5p expression. Up-regulation of miR-125a-5p after TLR2/4 activation requires the adaptor MYD88 but not TRIF. Overexpression of miR-125a-5p diminished M1 phenotype expression induced by LPS but promoted M2 marker expression induced by IL-4. In contrast, knockdown of miR-125a-5p promoted M1 polarization and diminished IL-4-induced M2 marker expression. We found that miR-125a-5p targets KLF13, a transcriptional factor that has an important role in T lymphocyte activation and inflammation. KLF13 knockdown had similar effects on M1 activation as did miR-125a-5p overexpression. In addition, miR-125a-5p regulates phagocytic and bactericidal activities of macrophages. Our data suggest that miR-125a-5p has an important role in suppressing classical activation of macrophages while promoting alternative activation.

Keywords: Inflammation; KLF13; Kruppel-like Factor (KLF); Macrophage Polarization; Macrophages; MicroRNA; Phagocytosis; Toll-like Receptors (TLR).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Vesicular Transport / deficiency
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Escherichia coli / immunology
  • Gene Knockdown Techniques
  • Inflammation / genetics*
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Kruppel-Like Transcription Factors / antagonists & inhibitors
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Macrophage Activation / genetics*
  • Macrophage Activation / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics*
  • MicroRNAs / immunology
  • MicroRNAs / metabolism*
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Up-Regulation


  • Adaptor Proteins, Vesicular Transport
  • Cell Cycle Proteins
  • Klf13 protein, mouse
  • Kruppel-Like Transcription Factors
  • MicroRNAs
  • Mirn125 microRNA, mouse
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Repressor Proteins
  • TICAM-1 protein, mouse
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4

Associated data

  • GEO/GSE46085