Hyperglycemia acts in synergy with hypoxia to maintain the pro-inflammatory phenotype of macrophages.
In: PLoS ONE, Jg. 14 (2019-08-14), Heft 8, S. 1-17
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Zugriff:
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 downregulated 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 hypoxia was combined with a high glucose concentration. In contrast, hyperglycemia and hypoxia 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. [ABSTRACT FROM AUTHOR]
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Hyperglycemia acts in synergy with hypoxia to maintain the pro-inflammatory phenotype of macrophages.
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Autor/in / Beteiligte Person: | Morey, Mangesh ; O'Gaora, Peadar ; Pandit, Abhay ; Hélary, Christophe |
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Zeitschrift: | PLoS ONE, Jg. 14 (2019-08-14), Heft 8, S. 1-17 |
Veröffentlichung: | 2019 |
Medientyp: | academicJournal |
ISSN: | 1932-6203 (print) |
DOI: | 10.1371/journal.pone.0220577 |
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