Myeloid cell expressed proprotein convertase FURIN attenuates inflammation

Oncotarget. 2016 Aug 23;7(34):54392-54404. doi: 10.18632/oncotarget.11106.


The proprotein convertase enzyme FURIN processes immature pro-proteins into functional end- products. FURIN is upregulated in activated immune cells and it regulates T-cell dependent peripheral tolerance and the Th1/Th2 balance. FURIN also promotes the infectivity of pathogens by activating bacterial toxins and by processing viral proteins. Here, we evaluated the role of FURIN in LysM+ myeloid cells in vivo. Mice with a conditional deletion of FURIN in their myeloid cells (LysMCre-fur(fl/fl)) were healthy and showed unchanged proportions of neutrophils and macrophages. Instead, LysMCre-fur(fl/fl) mice had elevated serum IL-1β levels and reduced numbers of splenocytes. An LPS injection resulted in accelerated mortality, elevated serum pro-inflammatory cytokines and upregulated numbers of pro-inflammatory macrophages. A genome-wide gene expression analysis revealed the overexpression of several pro-inflammatory genes in resting FURIN-deficient macrophages. Moreover, FURIN inhibited Nos2 and promoted the expression of Arg1, which implies that FURIN regulates the M1/M2-type macrophage balance. FURIN was required for the normal production of the bioactive TGF-β1 cytokine, but it inhibited the maturation of the inflammation-provoking TACE and Caspase-1 enzymes. In conclusion, FURIN has an anti-inflammatory function in LysM+ myeloid cells in vivo.

Keywords: FURIN; Immune response; Immunity; Immunology and Microbiology Section; LysM; TGF-β1; cytokine; macrophage.

MeSH terms

  • ADAM17 Protein / metabolism
  • Animals
  • Caspase 1 / metabolism
  • Furin / physiology*
  • Gene Expression Regulation
  • Inflammation / prevention & control*
  • Interleukin-1beta / blood
  • Lipopolysaccharides / toxicity
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / enzymology*
  • Transforming Growth Factor beta1 / metabolism


  • Interleukin-1beta
  • Lipopolysaccharides
  • Transforming Growth Factor beta1
  • Furin
  • Caspase 1
  • ADAM17 Protein