title: 1, 25(OH)2D3-induced interaction of vitamin D receptor with p50 subunit of NF-κB suppresses the interaction between KLF5 and p50, contributing to inhibition of LPS-induced macrophage proliferation.
abstract: KLF5 and nuclear factor κB (NF-κB) regulate cell proliferation and inflammation. Vitamin D signaling through vitamin D receptor (VDR) exerts anti-proliferative and anti-inflammatory actions. However, an actual relationship between KLF5, NF-κB and VDR in the inflammation and proliferation of macrophages is still unclear. Here, we showed that LPS and proinflammatory cytokines stimulate KLF5 gene expression in macrophages, and that 1, 25(OH)2D3suppresses LPS-induced KLF5 expression and cell proliferation via upregulation of VDR expression. Mechanistic studies suggested that KLF5 interacts with p50 subunit of NF-κB to cooperatively induce the expressions of positive cell cycle regulators cyclin B1 and Cdk1/Cdc2 in LPS-treated macrophages. Further studies revealed that 1, 25(OH)2D3-induced interaction of VDR with p50 decreases LPS-induced interaction of KLF5 with p50. Collectively, we identify a novel regulatory pathway in which 1, 25(OH)2D3induces VDR expression and promotes VDR interaction with p50 subunit of NF-κB, which in turn attenuates the association of KLF5 with p50 subunit of NF-κB and thus exerts anti-inflammatory and anti-proliferative effects on macrophages.
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, PR China; School of Public Health, North China University of Science and Technology, Tangshan, Hebei, 063000, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: Ruo-Nan
authors.initials: RN
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Pediatrics, Handan First Hospital, 056000, PR China.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Yin
authors.affiliation: School of Public Health, North China University of Science and Technology, Tangshan, Hebei, 063000, PR China.
authors.forename: Disi
authors.initials: D
authors.lastname: Bai
authors.affiliation: School of Public Health, North China University of Science and Technology, Tangshan, Hebei, 063000, PR China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: Jin-Shui
authors.initials: JS
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, PR China. Electronic address: wjk@hebmu.edu.cn.
authors.forename: Jin-Kun
authors.initials: JK
authors.lastname: Wen
mesh_terms: D000818:Animals; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D000067996:RAW 264.7 Cells; D018167:Receptors, Calcitriol / Q000378:metabolism*; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D021122:Protein Subunits; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D
keywords: 1,25(OH)(2)D(3); KLF5; Macrophage; NF-κB; Proliferation; Vitamin D receptor