1, 25(OH) 2 D 3 -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
| Autor: | Ya Wen, Wei-na Yin, Ruo-nan Zhang, Disi Bai, Guo-ying Zheng, Dong Ma, Jin-kun Wen, Jin-shui Li, Bin Zheng |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell growth Biophysics NF-κB Cell Biology Cell cycle Biology Biochemistry Calcitriol receptor Cell biology Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Downregulation and upregulation 030220 oncology & carcinogenesis Cancer research lipids (amino acids peptides and proteins) Cyclin B1 Molecular Biology Macrophage proliferation |
| Zdroj: | Biochemical and Biophysical Research Communications. 482:366-374 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2016.11.069 |
| Popis: | 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)2D3 suppresses 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)2D3 induces 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. |
| Databáze: | OpenAIRE |
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