Inhibition of TNF-alpha induced ICAM-1, VCAM-1 and E-selectin expression by selenium.
The initiation of an atherosclerotic lesion involves an endothelial cell pro-inflammatory state that recruits leukocytes and promotes their movement across the endothelium. These processes require endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-leukocyte adhesion molecule-1 (E-selectin). Tumor necrosis factor-alpha (TNF-alpha) is a powerful inducer of these adhesion molecules. Selenium status is known to affect the rate of atherosclerosis. These experiments tested whether selenium alters cytokine-induced expression of these adhesion molecules. Human umbilical vein endothelial cells (HUVECs) were pretreated for 24 h with sodium selenite (0-2 microM) and then treated with 0 or 50 U/ml TNF-alpha in the presence of 0-2 microM selenite. ICAM-1, VCAM-1 and E-selectin were detected by ELISA and their mRNAs were evaluated by Northern blots. Selenite significantly inhibited TNF-alpha-induced expression of each adhesion molecule in a dose-dependent manner and reduced the level of the respective mRNAs. Nuclear factor-kappa B (NF-kappa B) is required for transcription of these adhesion molecule genes. Western blot analysis revealed that selenite did not inhibit the translocation of the p65 subunit of NF-kappa B to the nucleus. In conclusion, these data indicate selenium can modulate cytokine-induced expression of ICAM-1, VCAM-1 and E-selectin in HUVECs without interfering with translocation of NF-kappa B.
Zhang
Fan
F
Department of Pharmaceutical and Biomedical Sciences, The University of Georgia, Athens, GA 30602, USA.
Yu
Wei
W
Hargrove
James L
JL
Greenspan
Phillip
P
Dean
Roger G
RG
Taylor
Ethan W
EW
Hartle
Diane K
DK
D000704:Analysis of Variance; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D019040:E-Selectin / Q000032:analysis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis* / Q000187:drug effects; D011336:Probability; D012643:Selenium / Q000494:pharmacology; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism
D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D012643:Selenium