Estrogen signaling differentially alters iron metabolism in monocytes in an Interleukin 6-dependent manner.

Estrogen signaling differentially alters iron metabolism in monocytes in an Interleukin 6-dependent manner. Immunobiology. 2020 Sep;225(5):151995 Authors: Bajbouj K, Shafarin J, Muhammad JS, Ali A, Unnikannan H, Suleiman B, Al-Jabi N, Menon K, Hamad M Abstract The ability of monocytes to release or sequester iron affects their role in cancer and inflammation. Previous work has shown that while IL-6 upregulates hepcidin synthesis and enhances iron sequestration, E2 reduces hepcidin synthesis and increases iron release. Given that E2 upregulates IL-6 production in monocytes, it is likely that the exact effect of E2 on iron metabolism in monocytes is shaped by its effect on IL-6 expression. To address this issue, the expression of key iron regulatory proteins was assessed in E2-treated U937, HuT-78, THP-1 and Hep-G2 cells. Iron status was also evaluated in U937 cells treated with the ERα agonist PPT, the ER antagonist ICI-182780, dexamethasone + E2, IL-6 + E2 and in IL-6-silenced U937 cells. E2 treatment reduced hepcidin synthesis in HuT-78, THP-1 and Hep-G2 cells but increased hepcidin synthesis and reduced FPN expression in U937 cells. E2-treated U937 cells also showed reduced HIF-1α and FTH expression and increased TFR1 expression, which associated with increased labile iron content as compared with similarly treated Hep-G2 cells. While treatment of U937 cells with interleukin 6 (IL-6) resulted in increased expression of hepcidin, ...
Source: Immunobiology - Category: Allergy & Immunology Authors: Tags: Immunobiology Source Type: research