Inhibition of TNF-α 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-α (TNF-α) 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 μM) and then treated with 0 or 50 U/ml TNF-α in the presence of 0–2 μM selenite. ICAM-1, VCAM-1 and E-selectin were detected by ELISA and their mRNAs were evaluated by Northern blots. Selenite significantly inhibited TNF-α-induced expression of each adhesion molecule in a dose-dependent manner and reduced the level of the respective mRNAs. Nuclear factor-κB (NF-κB) 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-κB 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-κB.