Diabetes during pregnancy influences Hofbauer cells, a subtype of placental macrophages, to acquire a pro-inflammatory phenotype

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1832

Article

Sisino, Giorgia^1,2,3  Bouckenooghe, Thomas^1,2,3  Aurientis, Sandra^1,2,3  Fontaine, Pierre^2,3,4  Storme, Laurent^1,2,3  Vambergue, Anne^1,2,3,4 

[1] EA4489, F-59000 Lille, France

[2] Univ Lille Nord France, F-59000 Lille, France

[3] UDSL, F-59000 Lille, France

[4] Univ Hosp, Dept Endocrinol, F-59000 Lille, France

关键词: Maternal diabetes;    Placenta;    Hofbauer cells;    High glucose;    M1-M2 macrophages;    Inflammation;   

DOI  :  10.1016/j.bbadis.2013.07.009

来源: Elsevier

【 摘 要 】

Growing evidence indicates that maternal pathophysiological conditions, such as diabetes, influence fetal growth and could program metabolic disease in adulthood. Placental cells, particularly Hofbauer cells (HBCs), which are placental macrophages characterized by an anti-inflammatory profile (M2), can sense the modified maternal environment. The goal of this study was to investigate the direct effect of hyperglycemia on HBCs. We studied, at mRNA and protein levels, some markers of M2 and M1 (pro-inflammatory) macrophages in placentae from control and diabetic patients to assess the balance between pro- and anti-inflammatory macrophages: an imbalance of M2 to M1 macrophages has been observed in humans. We used pregnant rats, receiving a single injection of streptozotocin (STZ), as a model of maternal diabetes. We noticed a M2-to-M1 macrophage unbalance as we observed in human. An in vitro model of isolated rat HBCs was used to identify the direct effects of high glucose. We found that high glucose stimulation activated genes belonging to TLR (Toll-Like Receptor)-dependent inflammatory pathways. Moreover, the HBCs stimulated by high glucose switched their M2 profile towards Ml, with increased expression of pro-inflammatory cytokines and markers. We also noticed that the oxidative-stress pathway was activated in response to high glucose driven by Hif-l alpha. In this study, we demonstrated that diabetes/hyperglycemia affect the anti-inflammatory profile of HBCs, by stimulating these cells to acquire an inflammatory profile leading to adverse consequences for the fetal-placental-maternal axis. (C) 2013 Elsevier B.V. All rights reserved.

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