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

• LPS induces Fli-1 expression in macrophages.
• Fli-1 is critical for LPS-induced IL-27 production in macrophages.
• LPS induces Fli-1to bind IL-27 p28 promoter.
• Fli-1 activates IL-27 p28 promoter cooperatively with IRF1.

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.