Garlic metabolites fail to inhibit the activation of the transcription factor NF-kappaB and subsequent expression of the adhesion molecule E-selectin in human endothelial cells.
BACKGROUND
The transcription factor NF-kappaB is suggested to play a pivotal role in atherogenesis by regulating the expression of proinflammatory gene products such as adhesion molecules. Garlic is consumed as food or dietary supplement in order to benefit from its antiatherogenic effect.


OBJECTIVE
This study addresses the question whether the garlic metabolites diallyldisulfide (DADS) and allylmercaptane (AM) influence the TNF-alpha-induced activation of NF-kappaB and the NF-kappaB-regulated endothelial gene product E-selectin in human umbilical endothelial cells (HUVECs).


METHODS
A putative effect of DADS and AM on NF-kappaB activity was examined by measuring NF-kappaB DNA binding activity by an electrophoretic mobility shift assay (EMSA) and on the NF-kappaB transactivation activity by a luciferase reporter gene assay. In addition, an effect of DADS and AM on the expression of the NF- kappaB-regulated gene product E-selectin was investigated by flow cytometry.


RESULTS
We show that neither DADS nor AM (up to 100 micro M) inhibit TNF-alpha (1-10 ng/ml)-induced NF-kappaB DNA binding nor NF-kappaB transactivation activity. The TNF-alpha-induced expression of the endothelial adhesion molecule E-selectin was not reduced in response to DADS or AM.


CONCLUSIONS
This study suggests that NF-kappaB is not a major target of garlic metabolites such as DADS or AM.
Dirsch
Verena M
VM
Dept. of Pharmacy, Center of Drug Research, Butenandtstr. 5-13, 81377, Munich, Germany. verena.dirsch@cup.uni-muenchen.de
Keiss
Hans-Peter
HP
Vollmar
Angelika M
AM
D000498:Allyl Compounds / Q000494:pharmacology; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005737:Garlic / Q000737:chemistry*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D000498:Allyl Compounds; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D013438:Sulfhydryl Compounds; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; C038491:allyl sulfide