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In vertebrates, cytokines can cause changes in iron levels in macrophages.
Changes in iron levels have been implicated in the binding of iron regulatory proteins (IRPs) to iron-responsive elements (IREs), which is part of the insect immune response [38].
The changes in iron levels in the placenta were very closely paralleled by the levels of HAMP expression, which may be merely responding to the tissue's fluctuation in iron concentration [69] or conversely, responding to a signal from outside the placenta, and in turn modulating iron export rates from this tissue to the fetal compartment [68].
Hfe has also been implicated in the iron signalling complex that modulates hepcidin transcription by sensing changes in iron levels [ 35].
To control for EPO-induced changes in iron levels in our in vitro models, we measured TFR1 mRNA expression in the same samples used for hepcidin and CEBPA/C ebpa assessment.
We have also observed increased NF-κB activity when iron was added to the cells or when TfR1 was overexpressed, demonstrating that NF-κB does sense changes in iron levels in the cell.
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This transcript was identified as part of the SciP regulon [ 28], and a recent study from our group showed that its expression is also regulated by Fur [ 40]. cspC expression does not respond to the change in iron levels and is not regulated by Fur (data not shown), so the decrease of the levels of this transcript could be via a decrease in its stabilization.
Hepcidin hyper-induction by quercetin correlated with changes in serum iron levels and transferrin saturation in the animals; the other polyphenols did not induce any changes in these parameters (Fig. 3A and B).
In contrast to TfR1, TfR2 does not vary in response to changes in intracellular iron levels.
In the latter, this induced changes in systemic iron levels.
In a separate analysis, this model with the Hepascore as the outcome measure will be extended to include the quantity of iron removed (calculated as 1 g iron per litre of RBCs removed by erythrocytapheresis) to determine whether there is an association between the change in Hepascore and the reduction in iron level.
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