Journal
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
Volume 67, Issue -, Pages -Publisher
ELSEVIER GMBH
DOI: 10.1016/j.jtemb.2021.126786
Keywords
Dysmetabolic iron overload syndrome; Metabolic syndrome; Macrophage polarization; Inflammation; Ferritin
Funding
- University Hospital of Clermont-Ferrand [Ruivard AOI 2013]
- French Society of Internal Medicine
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In patients with DIOS, impairment in macrophage polarization towards the M2 alternative phenotype was observed, but it was not associated with a pro-inflammatory profile. Compared to MetS, DIOS patients showed an increased expression of several genes related to iron metabolism, with an upregulation of transferrin receptor 1 (TFRC) suggesting a potential adaptive role in limiting iron toxicity.
Aims: Dysmetabolic iron overload syndrome (DIOS) is common but the clinical relevance of iron overload is not understood. Macrophages are central cells in iron homeostasis and inflammation. We hypothesized that iron overload in DIOS could affect the phenotype of monocytes and impair macrophage gene expression. Methods: This study compared 20 subjects with DIOS to 20 subjects with metabolic syndrome (MetS) without iron overload, and 20 healthy controls. Monocytes were phenotyped by Fluorescence-Activated Cell Sorting (FACS) and differentiated into anti-inflammatory M2 macrophages in the presence of IL-4. The expression of 38 genes related to inflammation, iron metabolism and M2 phenotype was assessed by real-time PCR. Results: FACS showed no difference between monocytes across the three groups. The macrophagic response to IL4-driven differentiation was altered in four of the five genes of M2 phenotype (MRC1, F13A1, ABCA1, TGM2 but not FABP4), in DIOS vs Mets and controls demonstrating an impaired M2 polarization. The expression profile of inflammatory genes was not different in DIOS vs MetS. Several genes of iron metabolism presented a higher expression in DIOS vs MetS: SCL11A2 (a free iron transporter, +76 %, p = 0.04), SOD1 (an antioxidant enzyme, +27 %, p = 0.02), and TFRC (the receptor 1 of transferrin, +59 %, p = 0.003). Conclusions: In DIOS, macrophage polarization toward the M2 alternative phenotype is impaired but not associated with a pro-inflammatory profile. The up regulation of transferrin receptor 1 (TFRC) in DIOS macrophages suggests an adaptive role that may limit iron toxicity in DIOS.
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