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Aggravated intestinal apoptosis by ClC‐3 deletion is lethal to mice endotoxemia
Author(s) -
Huang LinYan,
Li YuJie,
Li PengPeng,
Li HongChun,
Ma Ping
Publication year - 2018
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11025
Subject(s) - inflammation , apoptosis , wild type , knockout mouse , tumor necrosis factor alpha , intestinal permeability , chloride channel , immunology , biology , chemistry , medicine , endocrinology , microbiology and biotechnology , receptor , biochemistry , gene , mutant
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.