Lanthanum Chloride Inhibits LPS Mediated Expressions of Pro-Inflammatory Cytokines and Adhesion Molecules in HUVECs: Involvement of NF-?B-Jmjd3 Signaling.

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 µM LaCl3 for 30 min followed by 1 µg/ml LPS for 2 h. Pro-inflammatory cytokine and adhesion molecule expressions were determined by real-time RT-PCR and ELISA. NF-?B/p65 nuclear translocation was examined by immunofluorescence and immuno-blot, and its DNA-binding activity was measured by chemiluminescence. Recruitment of NF-?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 µM. LPS-mediated TNF-?, IL-1?, IL-6, MMP-9, and ICAM-1 production, nuclear translocation, and DNA-binding activity of NF-?B/p65, as well as Jmjd3 expression, were all reduced significantly by LaCl3. Furthermore, LaCl3 treatment significantly impaired LPS-induced enrichment of NF-?B/p65 to the promoter regions of TNF-?, MMP-9, IL-1?, ICAM-1, and IL-6; and of Jmjd3 to the promoter regions of TNF-?, MMP-9, IL-1?, and IL-6. H3K27me3 abundance in the promoter regions of TNF-? 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-?B and histone demethylase Jmjd3 are involved in this effect.