Mercury chloride activates the IFNγ-IRF1 signaling in myeloid progenitors and promotes monopoiesis in mice

Abstract

Inorganic mercury (Hg²⁺) is a highly toxic heavy metal in the environment. To date, the impacts of Hg²⁺ on the development of monocytes, or monopoiesis, have not been fully addressed. The aim of the present study was to investigate the impact of Hg²⁺ on monopoiesis. In this study, we treated B10.S mice and DBA/2 mice with 10 μM or 50 μM HgCl₂ via drinking water for 4 wk, and we then evaluated the development of monocytes. Treatment with 50 μM HgCl₂, but not 10 μM HgCl₂, increased the number of monocytes in the blood, spleen and bone marrow (BM) of B10.S mice. Accordingly, treatment with 50 μM HgCl₂, but not 10 μM HgCl₂, increased the number of common myeloid progenitors (CMP) and granulocyte-macrophage progenitors (GMP) in the BM. Functional analyses indicated that treatment with 50 μM HgCl₂ promoted the differentiation of CMP and GMP to monocytes in the BM of B10.S mice. Mechanistically, treatment with 50 μM HgCl₂ induced the production of IFNγ, which activated the Jak1/3-STAT1/3-IRF1 signaling in CMP and GMP and enhanced their differentiation potential for monocytes in the BM, thus likely leading to increased number of mature monocytes in B10.S mice. Moreover, the increased monopoiesis by Hg²⁺ was associated with the increased inflammatory status in B10.S mice. In contrast, treatment with 50 μM HgCl₂ did not impact the monopoiesis in DBA/2 mice. Our study reveals the impact of Hg on the development of monocytes.

Keywords: IFNγ; IRF1; Jak/STAT; Mercury chloride; Monopoiesis.