Anemia of inflammation is a prevalent comorbidity in patients with chronic inflammatory disorders. Inflammation causes hypoferremia and iron-restricted erythropoiesis by limiting ferroportin (FPN)-mediated iron export from macrophages that recycle senescent erythrocytes. Macrophage cell surface expression of FPN is reduced by hepcidin-induced degradation and/or by repression of FPN (Slc40a1) transcription via cytokine and Toll-like receptor (TLR) stimulation. Although the mechanisms underlying hepcidin-mediated control of FPN have been extensively studied, those inhibiting Slc40a1 messenger RNA (mRNA) expression remain unknown. We applied targeted RNA interference and pharmacological screens in macrophages stimulated with the TLR2/6 ligand FSL1 and identified critical signaling regulators of Slc40a1 mRNA repression downstream of TLRs and NF-
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