Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 482, Issue 2, Pages 366-374Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.11.069
Keywords
1,25(OH)(2)D-3; Vitamin D receptor; NF-kappa B; KLF5; Macrophage; Proliferation
Categories
Funding
- National Natural Science Foundation of China [31671182, 31271396, 31271224, 31301136]
- Hebei Key Scientific and Technological Project [13967607D]
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KLF5 and nuclear factor kappa B (NF-kappa B) 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-kappa B 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)(2)D-3 suppresses LPS-induced KLF5 expression and cell proliferation via upregulation of VDR expression. Mechanistic studies suggested that KLF5 interacts with p50 subunit of NF-kappa B 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)(2)D-3-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)(2)D-3 induces VDR expression and promotes VDR interaction with p50 subunit of NF-kappa B, which in turn attenuates the association of KLF5 with p50 subunit of NF-kappa B and thus exerts anti-inflammatory and anti-proliferative effects on macrophages. (C) 2016 Elsevier Inc. All rights reserved.
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