Transcriptomics,Genomics

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Myeloid Cell Expressed Proprotein Convertase FURIN Attenuates Inflammation


ABSTRACT: 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. Overall design: Two biological replicates of FURIN KO and WT peritoneal macrophages were left unstimulated or were stimulated for 1, 4 and 24 hours with LPS.

INSTRUMENT(S): Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version)

SUBMITTER: Ville Kalle Tapio Kytölä  

PROVIDER: GSE84117 | GEO | 2016-12-30

SECONDARY ACCESSION(S): PRJNA328082

REPOSITORIES: GEO

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