Lactate and IL6 define separable paths of inflammatory metabolic adaptation.
Sci Adv
; 7(26)2021 06.
Article
em En
| MEDLINE
| ID: mdl-34162546
ABSTRACT
Lactate is an end point of Warburg-type metabolism found in inflammatory macrophages. Recently, lactate was shown to modify histones of lipopolysaccharide (LPS)-activated macrophages in a time-dependent way and promote the expression of genes linked to tissue repair, including arginase-1 (Arg1). We tested the interrelationships between histone lactylation (Kla) and tissue reparative gene expression and found that Kla was uncoupled from changes in gene expression linked to resolving M2 macrophage activation but correlated with Arg1 expression. LPS-induced Arg1 was instead dependent on autocrine-paracrine interleukin-6 (IL6) production, the IL6 receptor, and Stat3 signal transduction. We found that Kla increases as macrophages prepare to die under inflammatory stress, and Kla was absent in macrophages that cannot generate reactive nitrogen or have defects in diverse macrophage death pathways. Thus, Kla is a consequence rather than a cause of macrophage activation but occurs coincidently with an IL6- and Arg1-dependent metabolic rewiring under inflammatory duress.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-6
/
Ácido Láctico
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha