Induction of Nramp2 in activated mouse macrophages is dissociated from regulation of the Nramp1, classical inflammatory genes, and genes involved in iron metabolism.
Nramp2 is a widely expressed metal-ion transporter that is involved in dietary iron absorption in the duodenum and iron uptake from transferrin in peripheral tissues. Nramp1 is a related gene involved in regulation of host pathogen interaction. Nramp2 has at least two alternatively spliced isoforms, one of which contains an iron-responsive element in its 3'-untranslated region. In this study, we investigated the regulation of both isoforms of Nramp2 in activated primary macrophages from mouse strains with wild-type (Bcg(r)) or mutant (Bcg(s)) alleles. The Nramp2-IRE and/or -nonIRE transcripts were up-regulated in all mouse strains analyzed after treatment with interferon-gamma and lipopolysaccharide. cDNA microarray analysis revealed that Nramp2 regulation is controlled discordantly from other iron-regulated genes and classical macrophage-activation genes in different mouse strains. We suggest that Nramp2 is regulated independently of known iron-responsive genes in macrophages, and its function in host defense is unrelated to Nramp1.
Wardrop
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SL
Institute of Molecular Biosciences and ARC Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane, Australia.
Wells
C
C
Ravasi
T
T
Hume
D A
DA
Richardson
D R
DR
D000818:Animals; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D007501:Iron; D033862:Iron-Binding Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2