Wnt signaling enhances macrophage responses to IL-4 and promotes resolution of atherosclerosis.
Elife
; 102021 03 15.
Article
en En
| MEDLINE
| ID: mdl-33720008
ABSTRACT
Atherosclerosis is a disease of chronic inflammation. We investigated the roles of the cytokines IL-4 and IL-13, the classical activators of STAT6, in the resolution of atherosclerosis inflammation. Using Il4-/-Il13-/- mice, resolution was impaired, and in control mice, in both progressing and resolving plaques, levels of IL-4 were stably low and IL-13 was undetectable. This suggested that IL-4 is required for atherosclerosis resolution, but collaborates with other factors. We had observed increased Wnt signaling in macrophages in resolving plaques, and human genetic data from others showed that a loss-of-function Wnt mutation was associated with premature atherosclerosis. We now find an inverse association between activation of Wnt signaling and disease severity in mice and humans. Wnt enhanced the expression of inflammation resolving factors after treatment with plaque-relevant low concentrations of IL-4. Mechanistically, activation of the Wnt pathway following lipid lowering potentiates IL-4 responsiveness in macrophages via a PGE2/STAT3 axis.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Interleucina-4
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Aterosclerosis
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Vía de Señalización Wnt
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Macrófagos
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Elife
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos