title: Abrogating ClC-3 Inhibits LPS-induced Inflammation via Blocking the TLR4/NF-κB Pathway.
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.
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Nan-Lin
authors.initials: NL
authors.lastname: Xiang
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yun-Jian
authors.initials: YJ
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: You-Wei
authors.initials: YW
authors.lastname: Huang
authors.affiliation: Department of Developmental and Regenerative Biology, Jinan University, Guangzhou 510632, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Zhi-Quan
authors.initials: ZQ
authors.lastname: Bai
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.|Department of Key Laboratory for Environmental Exposure and Health, Environment College, Jinan University, Guangzhou 510632, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Guangzhou Overseas Chinese Hospital, Jinan University, Guangzhou 510632, China.|Department of Cardiology, the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000067996:RAW 264.7 Cells; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018118:Chloride Channels; C115376:ClC-3 channel; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid