Sulforaphane inhibition of monocyte adhesion via the suppression of ICAM-1 and NF-kappa B is dependent upon glutathione depletion in endothelial cells

Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables. We here report that SFN is a potent inhibitor of LPS-induced monocyte adhesion, and also blocks the gene expression of the adhesion molecule, ICAM-1, at non-toxic concentrations. Downstream of ICAM-1, NF-kappa B activity was also found to be abolished in a dose-and time-dependent by SFN in LPS-treated endothelial cells (ECs). SFN exerts its suppressive effects on NF-kappa B activity in these cells by preventing the degradation of I kappa B-alpha. Interestingly, the inhibition of P65 translocation and I kappa B-alpha degradation was reversed slightly after 12 hours pretreatment. The intracellular GSH levels in SFN-treated ECs were observed to be reduced, the time course coincident with the suppression of P65 translocation and I kappa B-alpha degradation. NAC and GSH reverse the inhibitory effects of SFN upon p65 translocation and I kappa B-alpha degradation when preincubated with this agent. Furthermore, the use of BSO to decrease intracellular GSH levels further enhanced the effects of SFN. These data thus suggest that the anti-inflammatory mechanisms of SFN are dependent upon intracellular glutathione level. (C) 2007 Elsevier Inc. All rights reserved.