Lactate-induced mtDNA Accumulation Activates cGAS-STING Signaling and the Inflammatory Response in Sjögren's Syndrome.
Int J Med Sci
; 20(10): 1256-1271, 2023.
Article
em En
| MEDLINE
| ID: mdl-37786436
ABSTRACT
Acinar epithelial cell atrophy in secretory glands is a hallmark of primary Sjögren's syndrome (pSS), the cause of which is far from elucidated. We examined the role of acinar atrophy by focusing on the metabolism of glandular epithelial cells and mitochondria in the pSS environment. After confirming the presence of a high-lactate environment in the labial glands of human pSS patients, we used the A253 cell line and NOD/Ltj mice as models to investigate the metabolic changes in salivary gland epithelial cells in a high-lactate environment in vitro and in vivo. We found that epithelial cells produced high levels of IL-6, IL-8, IFN-α, IFN-ß and TNF-α and exhibited significant NF-κB and type I IFN-related pathway activation. The results confirmed that lactate damaged mitochondrial DNA (mtDNA) and led to its leakage, which subsequently activated the cGAS-STING pathway. Inflammatory cytokine production and pathway activation were inhibited in vivo and in vitro by the lactate scavenger sodium dichloroacetate (DCA). Our study provides new insights into the etiology and treatment of pSS from the perspective of cell metabolism.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Sjogren
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Med Sci
Assunto da revista:
MEDICINA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China