Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages.
Science
; 356(6337): 513-519, 2017 05 05.
Article
en En
| MEDLINE
| ID: mdl-28473584
ABSTRACT
Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays a critical role in the control of immune responses. However, its mechanisms of action remain poorly understood. Here, we show that IL-10 opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, we show that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. Furthermore, IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4. Consequently, IL-10 promotes mitophagy that eliminates dysfunctional mitochondria characterized by low membrane potential and a high level of reactive oxygen species. In the absence of IL-10 signaling, macrophages accumulate damaged mitochondria in a mouse model of colitis and inflammatory bowel disease patients, and this results in dysregulated activation of the NLRP3 inflammasome and production of IL-1ß.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedades Inflamatorias del Intestino
/
Interleucina-10
/
Colitis
/
Intestinos
/
Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos