Kupffer Cell-Derived TNF-α Triggers the Apoptosis of Hepatic Stellate Cells through TNF-R1/Caspase 8 due to ER Stress.
Biomed Res Int
; 2020: 8035671, 2020.
Article
em En
| MEDLINE
| ID: mdl-32802876
ABSTRACT
PURPOSE:
To investigate the roles of ER stress in Kupffer cells (KCs) and KC-derived TNF-α in the apoptosis of hepatic stellate cells (HSCs).METHODS:
A rat model of liver fibrosis was established. Liver and blood serum samples were collected. Liver function assays, Masson staining, Sirius Red staining, ELISAs, and TUNEL and immunohistochemical staining were performed. Liver function, liver fibrosis, KC phenotype, inflammatory factors, and number of active HSCs were investigated. KCs were isolated, treated with tunicamycin, and then, cocultured with primary hepatic stellate cells. ELISAs, immunofluorescence staining, flow cytometry, and Western blotting were performed. KC phenotype, inflammatory factors, HSC apoptosis, and TNF-R1/caspase 8 pathway activity were examined.RESULT:
s. ER stress in KCs reduced the levels of liver function markers, reduced the degree of liver fibrosis, and increased the number of KCs with the M1 phenotype and the expression of TNF-α. The increase in KC-derived TNF-α reduced the number of active HSCs and increased the activity of TNF-R1/caspase 8. Furthermore, ER stress in KCs promoted the polarization of KCs towards the M1 phenotype and increased the expression of TNF-α. The increase in KC-derived TNF-α triggered the apoptosis of HSCs and the activation of TNF-R1/caspase 8 in vitro, which was consistent with the in vivo results.CONCLUSION:
ER stress in KCs promotes the polarization of these cells towards the M1 phenotype and increases the expression of TNF-α. Then, the increase in KC-derived TNF-α triggers the apoptosis of HSCs through TNF-R1/caspase 8.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Necrose Tumoral alfa
/
Apoptose
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Receptores Tipo I de Fatores de Necrose Tumoral
/
Caspase 8
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Células Estreladas do Fígado
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Estresse do Retículo Endoplasmático
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Células de Kupffer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article