Does iron overload in metabolic syndrome affect macrophage profile? A case control study

被引:5
作者
Lahaye, Clement [1 ]
Gladine, Cecile [2 ]
Pereira, Bruno [3 ]
Berger, Juliette [4 ]
Chinetti-Gbaguidi, Giulia [5 ]
Lain, Fabrice [6 ,7 ]
Mazur, Andrzej [2 ]
Ruivard, Marc [8 ]
机构
[1] Univ Clermont Auvergne, CHU Clermont Ferrand, Hop Estaing,INRAE,UNH, Serv Med Interne,Unite Nutr Humaine,CRNH Auvergne, F-63000 Clermont Ferrand, France
[2] Univ Clermont Auvergne, INRAE, UNH, Unite Nutr Humaine,CRNH Auvergne, F-63000 Clermont Ferrand, France
[3] Univ Clermont Auvergne, CHU Clermont Ferrand, Unite Biostat, F-63000 Clermont Ferrand, France
[4] Univ Clermont Auvergne, CHU Clermont Ferrand, Hop Estaing, Lab Hematol, F-63000 Clermont Ferrand, France
[5] Univ Cote DAzur, CHU Nice, INSERM, C3M, F-06000 Nice, France
[6] CHU Rennes, INSERM, CIC 1414, F-35000 Rennes, France
[7] CHU Rennes, Liver Unit, F-35000 Rennes, France
[8] Univ Clermont Auvergne, CHU Clermont Ferrand, Hop Estaing, Serv Med Interne, F-63000 Clermont Ferrand, France
关键词
Dysmetabolic iron overload syndrome; Metabolic syndrome; Macrophage polarization; Inflammation; Ferritin; HUMAN MONOCYTES; PPAR-GAMMA; EXPRESSION; RESISTANCE; CELLS;
D O I
10.1016/j.jtemb.2021.126786
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:8
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