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(Journal of Leukocyte Biology. 2002;71:99-106.)
© 2002 by Society for Leukocyte Biology

Induction of Nramp2 in activated mouse macrophages is dissociated from regulation of the Nramp1, classical inflammatory genes, and genes involved in iron metabolism

S. L. Wardrop^*, C. Wells^*, T. Ravasi^*, D. A. Hume^* and D. R. Richardson

^* Institute of Molecular Biosciences and ARC Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane, Australia; and
The Heart Research Institute, Camperdown, Sydney, Australia

Correspondence: Professor D. A. Hume, Institute of Molecular Biosciences, University of Queensland, Brisbane 4072, Australia. E-mail: d.hume{at}imb.uq.edu.au

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- 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.

Key Words: transferrin receptor • ferritin • 3'UTR • iNOS

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