Aggravated intestinal apoptosis by ClC-3 deletion is lethal to mice endotoxemia.
Cell Biol Int
; 42(10): 1445-1453, 2018 Sep.
Article
en En
| MEDLINE
| ID: mdl-29972266
ABSTRACT
Our previous study found that ClC-3 chloride channel functioned differently in the vascular and intestinal inflammation, the loss of ClC-3 reduced vascular inflammation but exacerbated intestinal inflammation. To furtherly clarify the role of ClC-3 chloride channels in systemic inflammation, we used LPS-induced endotoxemia model to investigate the response of wild-type and ClC-3 knockout mice to systemic inflammation. The results showed that in the LPS-induced endotoxemia model, the mortality of mice with ClC-3 deletion was significantly higher than that of wild-type mice. The liver and lung inflammations in mice with ClC-3 deletion were significantly less than those in wild-type mice, and the levels of TNF-α and MIP-2 in serum were lower than those of wild-type mice. However, intestinal inflammatory cytokines contents and intestinal permeability were higher than wild-type mice. After transfection of THP-1 cells with ClC-3 siRNA, the contents of TNF-α and IL-8 in LPS-induced cell supernatants were significantly decreased. Further experiments revealed that the level of Bax and Cleaved Caspase 3 in intestinal tissue of mice with ClC-3 deletion was significantly increased, while the level of Bcl2 did not change, which indicated that the intestinal apoptosis was increased after LPS-induced mice intestinal integrity destruction. Therefore, the regulation of intestinal tissue integrity by ClC-3 is crucial for maintaining LPS-induced survival in mice with endotoxemia.
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Bases de datos:
MEDLINE
Asunto principal:
Canales de Cloruro
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Biol Int
Año:
2018
Tipo del documento:
Article