Abstract
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-κB 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology*
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Chloride Channels / antagonists & inhibitors*
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Chloride Channels / genetics
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Chloride Channels / immunology
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Female
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Gene Expression Regulation
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / genetics
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Interleukin-1beta / immunology
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Lipopolysaccharides
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Male
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Mice
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / genetics
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NF-kappa B / immunology
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Peritonitis / chemically induced
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Peritonitis / drug therapy*
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Peritonitis / genetics
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Peritonitis / pathology
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RAW 264.7 Cells
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RNA, Small Interfering / genetics
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RNA, Small Interfering / immunology
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Signal Transduction
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Toll-Like Receptor 4 / antagonists & inhibitors*
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / immunology
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Chloride Channels
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ClC-3 channel
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IL1B protein, mouse
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Interleukin-1beta
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Lipopolysaccharides
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NF-kappa B
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RNA, Small Interfering
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Tlr4 protein, mouse
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Toll-Like Receptor 4
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid