title: Kir3.1 channel is functionally involved in TLR4-mediated signaling.
abstract: We aimed to study the involvement of Kir3.1 channel in TLR4-mediated signaling. LPS stimulation induced the recruitment of TLR4 and Kir3.1 into the lipid raft in THP-1 cells. Treatment with Tertiapin-Q, an inhibitor of Kir3.1, markedly abolished the recruitment of TLR4 into the lipid raft and inhibited the LPS-induced NF-κB activation, resulting in decreased production of TNF-α, IL-1β, and IL-6. To verify the specific role of the Kir3.1 channel, we generated Kir3.1-knockdown THP-1 cells. The Kir3.1(KD) THP-1 cells exhibited inhibition of NF-κB activation and production of these pro-inflammatory cytokines in response to TLR4 stimulation. Taken together, our results demonstrate that the Kir3.1 channel is involved in the TLR4-mediated signal at an early event by facilitating the recruitment of TLR4 into lipid raft.
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Cheoncheon-Dong 300, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, Republic of Korea.
authors.forename: Hee-Yeon
authors.initials: HY
authors.lastname: Jo
authors.forename: So Yong
authors.initials: SY
authors.lastname: Kim
authors.forename: Sooyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Sookyoung
authors.initials: S
authors.lastname: Jeong
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Tong Mook
authors.initials: TM
authors.lastname: Kang
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Lee
mesh_terms: D001514:Bee Venoms / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D001514:Bee Venoms; D016207:Cytokines; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C029738:tertiapin