The Role and Mechanism of VCAM-1 in 2-Methoxyestradiol Inhibiting Monocyte-Endothelial Cell Adhesions

Abstract

2-Methoxyestradiol (2-ME) is a major endogenous metabolite of estrogen, which formed by catalysis of cytochrome P450 (CYP450) and catechins-O-methoxy transferase (COMT), has an important role in atherosclerosis (AS), but the underlying mechanisms remain obscure. In our work, we investigated the role and mechanism of 2-ME inhibiting monocyte-endothelial cell adhesion. In vitro studies using monocyte-endothelial cell adhesion assay and cell immunofluorescence method showed that lipopolysaccharide (LPS) promoted monocyte-endothelial cell adhesion, these effects were blocked by 2-ME through a dose- and time-dependent manner. Furthermore, Vascular cell adhesion molecular-1 (VCAM-1) specific antibody (anti- VCAM-1, 1:1000) were pre-incubated the cells for 48 h, and by monocyte-endothelial cell adhesion experiment, results showed that anti-VCAM-1 can significantly inhibit the LPS-induced monocyte-endothelial cell adhesion, indicating VCAM-1 may be the key molecule of the LPS-nduced cell adhesion. Moreover, through Western Blot and monocyte-endothelial cell adhesion assay observing, results showed that 2-ME (10^(-5) M) pretreatment for 48 h was strongest inhibited the expression of VCAM-1, NF-_κBp65 nucleus protein and nuclear translocation on LPS-induced endothelial cell. In conclusion, 2-ME has the effect on monocytes-endothelial cell adhesion, and the mechanism is that inhibiting the role of the nuclear transcription factor NF-_κBp65 and down regulation the expression of VCAM-1. This study will be helpful for further clarify the mechanism of 2-ME anti-AS, and can be used as a new type of clinical drug development.

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