The maintenance of
iron homeostasis is critical as both
iron deficiency and
iron excess are deleterious. In mammals,
iron homeostasis is regulated systemically by the
iron-
hormone hepcidin, an
acute-phase protein secreted by the liver which inhibits
iron absorption and recycling. Cellularly, the interaction of
iron regulatory proteins (
IRP) 1 and 2 with
iron-responsive elements controls the expression of target mRNAs encoding
proteins of
iron acquisition, storage, utilization, and export. These processes critically affect
iron levels, which in turn impact on numerous aspects of
inflammation. To explore the role of IRP1 and IRP2 in
inflammation, IRP-deficient mice, i.e., mice with total and constitutive deficiency of either IRP, were subjected to acute aseptic local
inflammation.
Turpentine oil injection increases the expression of
acute phase proteins in the liver and
interleukin 6 levels in the serum of control mice. Both IRP-deficient mouse models mount the same responses, indicating that the treatment was efficient in all animals and that the
acute phase response does not require expression of both IRPs. As expected,
turpentine oil treatment enhances
hepcidin mRNA expression in the liver of wild-type mice, associated with decreased serum
iron levels. Importantly, Irp1 (-/-) and Irp2 (-/-) animals, respectively, display quantitatively similar
hepcidin mRNA induction and the appropriate reduction of the serum
iron values. Our data indicate that the response of Irp1 (-/-) and Irp2 (-/-) mice to acute local
inflammation is largely preserved.