Transducin-like enhancer of split-1 is expressed and functional in human macrophages

FEBS Lett. 2016 Jan;590(1):43-52. doi: 10.1002/1873-3468.12029. Epub 2015 Dec 30.

Abstract

Macrophages display heterogeneous phenotypes, including the classical M1 proinflammatory and the alternative M2 anti-inflammatory polarization states. The transducin-like enhancer of split-1 (TLE1) is a transcriptional corepressor whose functions in macrophages have not been studied yet. We report that TLE1 is highly expressed in human alternative macrophages in vitro and in atherosclerotic plaques as well as in adipose tissue M1/M2 mixed macrophages. TLE1 silencing in alternative macrophages decreases the expression of the M2 markers IL-1Ra and IL-10, while it exacerbates TNFα and CCL3 induction by lipopolysaccharide. Hence, TLE1 is expressed in human macrophages where it has potential anti-inflammatory and alternative phenotype promoting properties.

Keywords: atherosclerosis; inflammation; macrophage polarization; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Body Mass Index
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cells, Cultured
  • Co-Repressor Proteins / antagonists & inhibitors
  • Co-Repressor Proteins / genetics
  • Co-Repressor Proteins / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / antagonists & inhibitors
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Interleukin-4 / pharmacology
  • Intra-Abdominal Fat / immunology
  • Intra-Abdominal Fat / metabolism
  • Intra-Abdominal Fat / pathology
  • Macrophage Activation* / drug effects
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Mice, 129 Strain
  • Obesity / blood
  • Obesity / immunology
  • Obesity / metabolism
  • Obesity / pathology
  • Plaque, Atherosclerotic / immunology
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • RNA Interference
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • Biomarkers
  • Co-Repressor Proteins
  • IL10 protein, human
  • IL1RN protein, human
  • IL4 protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Recombinant Proteins
  • Repressor Proteins
  • TLE1 protein, human
  • Tle1 protein, mouse
  • Interleukin-10
  • Interleukin-4