Abrogating ClC-3 Inhibits LPS-induced Inflammation via Blocking the TLR4/NF-κB Pathway

作者：Xiang, Nan-lin; Liu, Jun; Liao, Yun-jian; Huang, You-wei; Wu, Zheng; Bai, Zhi-quan; Lin, Xi; Zhang, Jian-hua^*

来源：Scientific Reports, 2016, 6(1): 27583.

DOI：10.1038/srep27583

• FACTOR-KAPPA-B
• CHLORIDE CHANNELS
• ACTIVATION

This study investigated the function of a chloride channel blocker, DIDS. Both in vitro and in vivo studies found that DIDS significantly inhibits lipopolysaccharide (LPS)-induced release of proin flammatory cytokines. Here, we show that DIDS inhibits LPS-induced inflammation, as shown by downregulation of inflammatory cytokines via inhibition of the TLR4/NF-kappa B pathway. Furthermore, we show that ClC-3siRNA transfection reduces LPS-induced pro-inflammation in Raw264.7 cells, indicating that ClC-3 is involved in the inhibitory effect of DIDS during LPS-induced cytokines release. In vivo, DIDS reduced LPS-induced mortality, decreased LPS-induced organic damage, and down-regulated LPS-induced expression of inflammatory cytokines. In sum, we demonstrate that ClC-3 is a pro-inflammatory factor and that inhibition of ClC-3 inhibits inflammatory induction both in vitro and in vivo, suggesting that ClC-3 is a potential anti-inflammatory target.

• 出版日期2016-7-1
• 单位暨南大学; 中山大学