Transcription factor Fli-1 positively regulates lipopolysaccharide-induced interleukin-27 production in macrophages

Mol Immunol. 2016 Mar:71:184-191. doi: 10.1016/j.molimm.2016.02.006. Epub 2016 Feb 20.

Abstract

IL-27 is an important regulator of TLR4-activated innate immune. The mechanism by which IL-27 production is regulated in TLR4-activated innate immune remains largely unclear. Here we show that expression of transcription factor Fli-1 at protein level is increased in macrophages following LPS stimulation. Fli-1 overexpression increases LPS-activated IL-27 production in macrophages. Consistently, Fli-1 knockdown inhibits LPS-induced IL-27 production in macrophages. Chromatin immunoprecipitation (ChIP) assay reveals that Fli-1 binds the promoter of IL-27 p28 subunit. Further experiments manifest that Fli-1 binds the region between -250 and -150 bp upstream of the transcriptional start site of p28 gene and increases p28 gene promoter-controlled transcription. These results demonstrate that Fli-1 positively regulates IL-27 production in TLR4-activated immune response by promoting transcription of IL-27 p28 gene.

Keywords: Fli-1; Gene transcription; IL-27; TLR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation / immunology*
  • HEK293 Cells
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • Immunoblotting
  • Interleukin-27 / biosynthesis*
  • Interleukin-27 / genetics
  • Lipopolysaccharides / immunology
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Proto-Oncogene Protein c-fli-1 / genetics
  • Proto-Oncogene Protein c-fli-1 / immunology*
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Transfection

Substances

  • Interleukin-27
  • Lipopolysaccharides
  • Proto-Oncogene Protein c-fli-1
  • RNA, Small Interfering