title: Defective splicing of the background K+channel K2P5.1 by the pre-mRNA splicing inhibitor, pladienolide B in lectin-activated mouse splenic CD4+T cells.
abstract: The two-pore domain K+channel K2P5.1 has been implicated in the pathogenesis of autoimmune diseases. We investigated the changes in K2P5.1 activity caused by a defect in normal pre-mRNA splicing in concanavalin A-activated mouse splenic CD4+T cells. The pre-mRNA splicing inhibitor, pladienolide B (1 μM) markedly decreased full-length K2P5.1 transcription in activated CD4+T cells, resulting in the disappearance of K2P5.1 activity and an imbalance in Th17 and Tregcytokines. These results suggest that the defect in K2P5.1 splicing by the pre-mRNA splicing inhibitor regulates pro- and/or anti-inflammatory cytokine production in K2P5.1-associated autoimmune diseases.
authors.affiliation: Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Tagishi
authors.affiliation: Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Endo
authors.affiliation: Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kito
authors.affiliation: Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Niwa
authors.affiliation: Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. Electronic address: sohya@mb.kyoto-phu.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohya
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D004852:Epoxy Compounds / Q000494:pharmacology*; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics* / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000187:drug effects* / Q000235:genetics
chemical_list: D004852:Epoxy Compounds; D018942:Macrolides; D024683:Potassium Channels, Tandem Pore Domain; D012322:RNA Precursors; C522342:pladienolide B
keywords: K(+) channel; K(2P)5.1; Pre-mRNA splicing inhibitor