Regulation of phorbol ester induced adhesion of human Jurkat T-cells to endothelial cells by the thiol antioxidant alpha-lipoate

Altered expression of cell adhesion molecules and changes in cell adhesion properties are implicated in various pathologic conditions. Regulation of adhesion processes by reactive oxygen species via specific redox dependent mechanisms have been reported. Thus, antioxidants are likely to have therapeutic application in pathologies involving changes in cell adhesion properties. The effects of alpha-lipoate in the regulation of phorbol 12-myristate 13-acetate (PMA)-induced adhesion molecule expression in human endothelial cells (ECV), and adherence of human Jurkat T cells to ECV cells were investigated. At clinically relevant doses lipoate down-regulated PMA (100 nM, 24 h)induced adhesion of Jurkat T-cells to ECV, and also decreased PMA induced ICAM-1 and VCAM-1 expression in ECV. Such inhibitory effects of lipoate were dose dependent in the concentration range 50-250 uM. Inhibition of PMA-induced adhesion molecule expression and cell-cell adhesion was more pronounced when a combination of antioxidants, lipoate and tocopherol, were used compared to the use of either of these antioxidant alone. The regulation of adhesion molecule expression and function by low concentration of antioxidants investigated was not NF-kappaB regulated or transcription dependent because no change in mRNA expression was observed. The inhibitory effect of low concentration of lipaote alone or in combination with tocopherol on agonist-induced adhesion processes observed in this study suggest marked therapeutic potential of these antioxidants.