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 proinflammatory 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.
Myeloid cell expressed proprotein convertase FURIN attenuates inflammation / Z.M. Cordova, A. Grönholm, V. Kytölä, V. Taverniti, S. Hämäläinen, S. Aittomäki, W. Niininen, I. Junttila, A. Ylipää, M. Nykter, M. Pesu. - In: ONCOTARGET. - ISSN 1949-2553. - 7:34(2016), pp. 54392-54404.
|Titolo:||Myeloid cell expressed proprotein convertase FURIN attenuates inflammation|
|Parole Chiave:||Cytokine; FURIN; immune response; immunity; immunology and microbiology section; LysM; Macrophage; TGF-β1; oncology|
|Settore Scientifico Disciplinare:||Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica|
Settore MED/04 - Patologia Generale
|Data di pubblicazione:||2016|
|Data ahead of print / Data di stampa:||5-ago-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.18632/oncotarget.11106|
|Appare nelle tipologie:||01 - Articolo su periodico|