Serine Metabolism Supports Macrophage IL-1ß Production.
Cell Metab
; 29(4): 1003-1011.e4, 2019 04 02.
Article
en En
| MEDLINE
| ID: mdl-30773464
ABSTRACT
Serine is a substrate for nucleotide, NADPH, and glutathione (GSH) synthesis. Previous studies in cancer cells and lymphocytes have shown that serine-dependent one-carbon units are necessary for nucleotide production to support proliferation. Presently, it is unknown whether serine metabolism impacts the function of non-proliferative cells, such as inflammatory macrophages. We find that in macrophages, serine is required for optimal lipopolysaccharide (LPS) induction of IL-1ß mRNA expression, but not inflammasome activation. The mechanism involves a requirement for glycine, which is made from serine, to support macrophage GSH synthesis. Cell-permeable GSH, but not the one-carbon donor formate, rescues IL-1ß mRNA expression. Pharmacological inhibition of de novo serine synthesis in vivo decreased LPS induction of IL-1ß levels and improved survival in an LPS-driven model of sepsis in mice. Our study reveals that serine metabolism is necessary for GSH synthesis to support IL-1ß cytokine production.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Serina
/
Interleucina-1beta
/
Macrófagos
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos