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PLoS One. 2013 Jul 29;8(7):e69694. doi: 10.1371/journal.pone.0069694. Print 2013.

A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice.

Author information

1
Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy.

Abstract

Control of systemic iron homeostasis is interconnected with the inflammatory response through the key iron regulator, the antimicrobial peptide hepcidin. We have previously shown that mice with iron deficiency anemia (IDA)-low hepcidin show a pro-inflammatory response that is blunted in iron deficient-high hepcidin Tmprss6 KO mice. The transcriptional response associated with chronic hepcidin overexpression due to genetic inactivation of Tmprss6 is unknown. By using whole genome transcription profiling of the liver and analysis of spleen immune-related genes we identified several functional pathways differentially expressed in Tmprss6 KO mice, compared to IDA animals and thus irrespective of the iron status. In the effort of defining genes potentially targets of Tmprss6 we analyzed liver gene expression changes according to the genotype and independently of treatment. Tmprss6 inactivation causes down-regulation of liver pathways connected to immune and inflammatory response as well as spleen genes related to macrophage activation and inflammatory cytokines production. The anti-inflammatory status of Tmprss6 KO animals was confirmed by the down-regulation of pathways related to immunity, stress response and intracellular signaling in both liver and spleen after LPS treatment. Opposite to Tmprss6 KO mice, Hfe(-/-) mice are characterized by iron overload with inappropriately low hepcidin levels. Liver expression profiling of Hfe(-/-) deficient versus iron loaded mice show the opposite expression of some of the genes modulated by the loss of Tmprss6. Altogether our results confirm the anti-inflammatory status of Tmprss6 KO mice and identify new potential target pathways/genes of Tmprss6.

PMID:
23922777
PMCID:
PMC3726786
DOI:
10.1371/journal.pone.0069694
[Indexed for MEDLINE]
Free PMC Article

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