Research Papers: Immunology:
Myeloid cell expressed proprotein convertase FURIN attenuates inflammation
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Zuzet Martinez Cordova1, Anna Grönholm1, Ville Kytölä2, Valentina Taverniti3, Sanna Hämäläinen1, Saara Aittomäki1, Wilhelmiina Niininen1, Ilkka Junttila4,5, Antti Ylipää2, Matti Nykter2 and Marko Pesu1,6
1 Team Immunoregulation, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland
2 Team Computational Biology, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland
3 Department of Food, Environmental and Nutritional Sciences (DeFENS), Division of Food Microbiology and Bioprocessing, Università degli Studi di Milano, Milan, Italy
4 School of Medicine, University of Tampere, Tampere, Finland
5 Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
6 Department of Dermatology, Tampere University Hospital, Tampere, Finland
Marko Pesu, email:
Keywords: cytokine, FURIN, LysM, macrophage, TGF-β1, Immunology and Microbiology Section, Immune response, Immunity
Received: February 25, 2016 Accepted: July 22, 2016 Published: August 05, 2016
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.
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