D-mannose suppresses macrophage IL-1ß production.
Nat Commun
; 11(1): 6343, 2020 12 11.
Article
em En
| MEDLINE
| ID: mdl-33311467
ABSTRACT
D-mannose is a monosaccharide approximately a hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of D-mannose inhibit tumour growth and stimulate regulatory T cell differentiation. It is not known whether D-mannose metabolism affects the function of non-proliferative cells, such as inflammatory macrophages. Here, we show that D-mannose suppresses LPS-induced macrophage activation by impairing IL-1ß production. In vivo, mannose administration improves survival in a mouse model of LPS-induced endotoxemia as well as decreases progression in a mouse model of DSS-induced colitis. Phosphomannose isomerase controls response of LPS-activated macrophages to D-mannose, which impairs glucose metabolism by raising intracellular mannose-6-phosphate levels. Such alterations result in the suppression of succinate-mediated HIF-1α activation, imposing a consequent reduction of LPS-induced Il1b expression. Disclosing an unrecognized metabolic hijack of macrophage activation, our study points towards safe D-mannose utilization as an effective intervention against inflammatory conditions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-1beta
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Ativação de Macrófagos
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Macrófagos
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Manose
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article