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Hyperglycemia acts in synergy with hypoxia to maintain the pro-inflammatory phenotype of macrophages

Abstract : Diabetic foot ulcers (DFUs) are characterized by a chronic inflammation state which prevents cutaneous wound healing, and DFUs eventually lead to infection and leg amputation. Macrophages located in DFUs are locked in an pro-inflammatory phenotype. In this study, the effect of hyperglycemia and hypoxia on the macrophage phenotype was analyzed. For this purpose, a microarray was performed to study the gene expression profile of macrophages cultivated in a high glucose concentration. Hyperglycemia upregulated the expression of pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, chemokines and down-regulated the expression of two receptors involved in phagocytosis (CD 36 and Class B scavenger type I receptors). In addition, eleven anti-apoptotic factors were upregulated whereas three pro-apoptotic genes were downregulated. Subsequently, the contribution of hypoxia and hyperglycemia to chronic inflammation and their potential synergistic effect was evaluated on activated THP-1 derived macrophages. A long term post activation effect (17 hours) was only observed on the upregulation of pro-inflammatory cytokines when hyp-oxia was combined with a high glucose concentration. In contrast, hyperglycemia and hyp-oxia did not have any effect on wound healing molecules such as TGF-β1. Taken together, the results show that hyperglycemia acts in synergy with hypoxia to maintain a chronic inflammation state in macrophages.
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Submitted on : Tuesday, October 1, 2019 - 12:26:32 PM
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Mangesh Morey, Peadar O'Gaora, Abhay Pandit, Christophe Hélary. Hyperglycemia acts in synergy with hypoxia to maintain the pro-inflammatory phenotype of macrophages. PLoS ONE, Public Library of Science, 2019, 14 (8), pp.e0220577. ⟨10.1371/journal.pone.0220577⟩. ⟨hal-02302288⟩

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