Sulforaphane inhibition of monocyte adhesion via the suppression of ICAM-1 and NF-kappaB 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- kappaB 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- kappaB activity in these cells by preventing the degradation of IkappaB-alpha. Interestingly, the inhibition of P65 translocation and IkappaB-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 IkappaB-alpha degradation. NAC and GSH reverse the inhibitory effects of SFN upon p65 translocation and IkappaB-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.
Liu
Yen-Chin
YC
Institute of Biotechnology, National Chiayi University, Chiayi, Taiwan.
Hsieh
Chia-Wen
CW
Weng
Yu-Chun
YC
Chuang
Shu-Hui
SH
Hsieh
Cheng-Yuan
CY
Wung
Being-Sun
BS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D015153:Blotting, Western; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D017879:Isothiocyanates; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013438:Sulfhydryl Compounds; D013454:Sulfoxides; D013861:Thiocyanates; D018799:Intercellular Adhesion Molecule-1; D008156:Luciferases; C016766:sulforaphane; D005978:Glutathione