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

Summary.

Background:

The transcription factor NF-κB 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.

Aim of the study:

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

Methods:

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

Results:

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

Conclusions:

This study suggests that NF-κB is not a major target of garlic metabolites such as DADS or AM.