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| Status |
Public on Dec 30, 2016 |
| Title |
Myeloid Cell Expressed Proprotein Convertase FURIN Attenuates Inflammation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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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| 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.
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| Contributor(s) |
Cordova ZM, Grönholm A, Kytölä V, Taverniti V, Hämäläinen S, Niininen W, Junttila I, Ylipää A, Nykter M, Pesu M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jul 07, 2016 |
| Last update date |
Jul 19, 2017 |
| Contact name |
Ville Kalle Tapio Kytölä |
| Organization name |
University of Tampere
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| Department |
BioMediTech
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| Lab |
Computational Biology
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| Street address |
Finn-Medi 2, Biokatu 8
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| City |
Tampere |
| ZIP/Postal code |
33720 |
| Country |
Finland |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA328082 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84117_RAW.tar |
55.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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