Hepcidin Induces M1 Macrophage Polarization in Monocytes or THP-1 Derived Macrophages

 Macrophage polarization plays a critical role in determining the inflammatory states. Hepcidin is a key negative regulator of iron homeostasis and functions. Although hepcidin has been shown to affect ferroportin expression in macrophages, whether it affects macrophage polarization is still largely unknown. 

 To address whether hepcidin induces macrophage polarization. 

 The expression of iNOS and CD206, and the ratio of IFN-γ vs IL-4 in THP-1 derived macrophages upon hepcidin stimulation were evaluated. Further detected was the percentage of CD16+ M1, CD23+ M1, CD10+ M2 and CCL22+ M2 cells in monocyte derived macrophages. 

 M1 associated molecules were increased in hepcidin-treated cells, yet M2 associated molecules were increased when hepcidin was neutralized. Concomitantly, we observed a significant increase in IRF3 phosphorylation in hepcidin-stimulated cells. However, STAT6 phosphorylation with hepcidin was neutralized. 

 Hepcidin is able to induce macrophage polarization towards M1 type, and might be utilized as a potential M1 macrophage agonist in clinical practice.