Tojapride prevents CaSR-mediated NLRP3 inflammasome activation in oesophageal epithelium irritated by acidic bile salts.
J Cell Mol Med
; 24(2): 1208-1219, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31859410
ABSTRACT
Impairment of the oesophageal epithelium in patients with reflux oesophagitis (RE) is a cytokine-mediated injury rather than a chemical burn. The present study was conducted to explore CaSR/NLRP3 inflammasome pathway activation and cytokines IL-1ß and IL-18 release in oesophageal epithelia injured by refluxates and the effects of Tojapride on that signal regulation. Using a modified RE rat model with Tojapride administration and Tojapride-pretreated SV40-immortalized human oesophageal epithelial cells (HET-1A) exposed to acidic bile salts pretreated with Tojapride, we evaluated the therapeutic effects of Tojapride on oesophageal epithelial barrier function, the expression of CaSR/NLRP3 inflammasome pathway-related proteins and the release of downstream cytokines in response to acidic bile salt irritation. In vivo, Tojapride treatment ameliorated the general condition and pathological lesions of the oesophageal epithelium in modified RE rats. In addition, Tojapride effectively blocked the CaSR-mediated NLRP3 inflammasome activation in modified RE rats. In vitro, Tojapride treatment can reverse the harmful effect of acidic bile salts, which reduced transepithelial electrical resistance (TEER), up-regulated the CaSR-mediated NLRP3 inflammasome pathway and increased caspase-1 activity, LDH release and cytokines secretion. Taken together, these data show that Tojapride can prevent CaSR-mediated NLRP3 inflammasome activation and alleviate oesophageal epithelial injury induced by acidic bile salt exposure.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos e Sais Biliares
/
Receptores de Detecção de Cálcio
/
Epitélio
/
Esôfago
/
Inflamassomos
/
Compostos Fitoquímicos
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China