Mechanisms of hepcidin induction.

<p>In hepatocytes, hepcidin induction is mediated primarily by BMP ligands binding with the HJV/BMPR complex. BMP6 is induced by high iron levels via an undefined mechanism. The protease TMPRSS6 inhibits hepcidin production by degrading HJV in response to low iron levels [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004998#ppat.1004998.ref095" target="_blank">95</a>]. High holo-transferrin levels stabilize the transferrin receptor 2 (Tfr2)/HFE complex, which promotes hepcidin induction, possibly by direct binding with HJV or BMPR [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004998#ppat.1004998.ref100" target="_blank">100</a>]. Hepcidin can also be induced by IL-6 via STAT3 signaling in hepatocytes and myeloid leukocytes. Inflammation can stimulate hepcidin production in myeloid leukocytes through pathogen recognition receptor signaling and through autocrine and paracrine production of IL-6.