Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 42, Issue 5, Pages 1713-1724Publisher
KARGER
DOI: 10.1159/000479439
Keywords
Lanthanum chloride; Nuclear factor kappa B; Jmjd3; H3K27Me3; Vascular inflammation
Categories
Funding
- National Natural Science Foundation of China [81160193]
- Fellowship for young scientist of Jiangxi Province [20122BCB23027]
- Science and Technology Planning Project of Health and Family Planning Commission of Jiangxi Province [20171061]
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Background/Aims: To investigate the regulation of LaCl3 on lipopolysaccharides (LPS)-induced pro-inflammatory cytokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs). Methods: Primary cultured HUVECs were pretreated with 2.5 mu M LaCl3 for 30 min followed by 1 mu g/ml LPS for 2 h. Pro-inflammatory cytokine and adhesion molecule expressions were determined by real-time RT-PCR and ELISA. NF-kappa B/p65 nuclear translocation was examined by immunofluorescence and immuno-blot, and its DNA-binding activity was measured by chemiluminescence. Recruitment of NF-kappa B/p65, Jmjd3, and H3K27me3 to gene promoter regions was determined by ChIP-qPCR. Results: LaCl3 exhibited no cytotoxic effects to primary HUVECs at concentrations <= 50 mu M. LPS-mediated TNF-alpha, IL-1 beta, IL-6, MMP-9, and ICAM-1 production, nuclear translocation, and DNA-binding activity of NF-kappa B/p65, as well as Jmjd3 expression, were all reduced significantly by LaCl3. Furthermore, LaCl3 treatment significantly impaired LPS-induced enrichment of NF-kappa B/p65 to the promoter regions of TNF-alpha, MMP-9, IL-1 beta, ICAM-1, and IL-6; and of Jmjd3 to the promoter regions of TNF-alpha, MMP-9, IL-1 beta, and IL-6. H3K27me3 abundance in the promoter regions of TNF-a and ICAM-1 increased significantly in following LaCl3 treatment. Conclusion: LaCl3 inhibits pro-inflammatory cytokine and adhesion molecule expressions induced by LPS in HUVECs. NF-kappa B and histone demethylase Jmjd3 are involved in this effect. (C) 2017 The Author(s) Published by S. Karger AG, Basel
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