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

摘要

>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-?oB/p65 nuclear translocation was examined by immunofluorescence and immuno-blot, and its DNA-binding activity was measured by chemiluminescence. Recruitment of NF-?oB/p65, Jmjd3, and H3K27me3 to gene promoter regions was determined by ChIP-qPCR. Results: LaCl₃ exhibited no cytotoxic effects to primary HUVECs at concentrations a‰¤ 50 ?μM. LPS-mediated TNF-?±, IL-1?2, IL-6, MMP-9, and ICAM-1 production, nuclear translocation, and DNA-binding activity of NF-?oB/p65, as well as Jmjd3 expression, were all reduced significantly by LaCl₃. Furthermore, LaCl₃ treatment significantly impaired LPS-induced enrichment of NF-?oB/p65 to the promoter regions of TNF-?±, MMP-9, IL-1?2, ICAM-1, and IL-6; and of Jmjd3 to the promoter regions of TNF-?±, MMP-9, IL-1?2, 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-?oB and histone demethylase Jmjd3 are involved in this effect.