Hyperglycemia acts in synergy with hypoxia to maintain the pro-inflammatory phenotype of macrophages.
Apoptosis
/ physiology
Cell Differentiation
/ drug effects
Cell Hypoxia
/ physiology
Cell Line, Tumor
Cytokines
/ metabolism
Diabetic Foot
/ metabolism
Glucose
/ administration & dosage
Humans
Hyperglycemia
/ metabolism
Interleukin-6
/ metabolism
Macrophages
/ drug effects
Tumor Necrosis Factor-alpha
/ metabolism
Up-Regulation
/ drug effects
Wound Healing
/ physiology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
09
04
2019
accepted:
18
07
2019
entrez:
16
8
2019
pubmed:
16
8
2019
medline:
7
3
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31415598
doi: 10.1371/journal.pone.0220577
pii: PONE-D-19-10106
pmc: PMC6695165
doi:
Substances chimiques
Cytokines
0
Interleukin-6
0
Tumor Necrosis Factor-alpha
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0220577Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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