Effects of sDR5-Fc fusion protein on infant mice with ulcerative colitis via the TRAIL-DR5 pathway.
J Biol Regul Homeost Agents
; 34(2): 525-533, 2020.
Article
em En
| MEDLINE
| ID: mdl-32425017
ABSTRACT
To explore effects of the sDR5-Fc fusion protein on ulcerative colitis of infant mice via the TRAIL-DR5 pathway, 50 female mice were randomly divided into 5 groups, i.e., control group (group A), dextran sulfate sodium group (group B), hIgG group (group C), 10 mg/kg sDR5-Fc group (group D), and 20 mg/ kg sDR5-Fc group (group E). The acute ulcerative colitis models were established. The weights and disease activity index (DAI) of each group were monitored daily. In addition, the pathological changes of colon tissues were observed by Hematoxylin-Eosin staining. The number of macrophages in colon tissues was detected by immunohistochemistry assay. Changes in the expression of inflammatory factors in colon tissues were detected by quantitative real-time polymerase chain reaction (PCR). Lipopolysaccharide (LPS) of different concentrations was utilized alone or in combination with TRAIL to stimulate the NCM460 cells. The activation of NLRP3 inflammasomes was detected by Western blot. The apoptosis of NCM460 cells was detected by flow cytometry. The results showed that in groups B and C, the body weights decreased, the DAI increased, the colon epithelial cells were injured, the inflammatory cells were infiltrated, and the macrophages in colon tissues increased significantly. In groups D and E, the body weights increased, the DAI decreased, the inflammation was significantly improved, the macrophages decreased significantly, and the gene expression levels of NLRP3, Caspase-1, and IL-1ß decreased significantly. Thus, sDR5-Fc could inhibit the activation of NLRP3 inflammasomes induced by TRAIL, thereby decreasing the apoptosis of NCM460 cells. In conclusion, the sDR5-Fc fusion protein could block the TRAIL-DR5 pathway to reduce the expression of NLRP3 inflammasomes, thereby improving ulcerative colitis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes de Fusão
/
Colite Ulcerativa
/
Ligante Indutor de Apoptose Relacionado a TNF
/
Receptores do Ligante Indutor de Apoptose Relacionado a TNF
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Animals
Idioma:
En
Revista:
J Biol Regul Homeost Agents
Assunto da revista:
BIOLOGIA
/
BIOQUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China