Rise and Fall of Kir2.2 Current by TLR4 Signaling in Human Monocytes: PKC-Dependent Trafficking and PI3K-Mediated PIP2 Decrease

The Journal of Immunology : Official Journal of the American Association of Immunologists
Kyung Soo KimSung Joon Kim

Abstract

LPSs are widely used to stimulate TLR4, but their effects on ion channels in immune cells are poorly known. In THP-1 cells and human blood monocytes treated with LPS, inwardly rectifying K(+) channel current (IKir,LPS) newly emerged at 1 h, peaked at 4 h (-119 ± 8.6 pA/pF), and decayed afterward (-32 ± 6.7 pA/pF at 24 h). Whereas both the Kir2.1 and Kir2.2 mRNAs and proteins were observed, single-channel conductance (38 pS) of IKir,LPS and small interfering RNA-induced knockdown commonly indicated Kir2.2 than Kir2.1. LPS-induced cytokine release and store-operated Ca(2+) entry were commonly decreased by ML-133, a Kir2 inhibitor. Immunoblot, confocal microscopy, and the effects of vesicular trafficking inhibitors commonly suggested plasma membrane translocation of Kir2.2 by LPS. Both IKir,LPS and membrane translocation of Kir2.2 were inhibited by GF109203X (protein kinase C [PKC] inhibitor) or by transfection with small interfering RNA-specific PKCε. Interestingly, pharmacological activation of PKC by PMA induced both Kir2.1 and Kir2.2 currents. The spontaneously decayed IKir,LPS at 24 h was recovered by PI3K inhibitors but further suppressed by an inhibitor of phosphatidylinositol(3,4,5)-trisphosphate (PIP3) phosphatase (phosph...Continue Reading

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Citations

Jun 30, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Yan-Rong ZhuDai-Min Zhang
Aug 4, 2018·Frontiers in Molecular Biosciences·Marcelle C RibeiroAna Acacia S Pinheiro
Nov 8, 2018·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·JooHan WooJoo Hyun Nam
Jan 23, 2020·International Journal of Molecular Sciences·Hyun Jin JungSeung Hyun Oh
Jan 5, 2021·Frontiers in Cellular Neuroscience·Ashwini HariharanThomas A Longden
Apr 16, 2021·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Louise Reilly, Lee L Eckhardt

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