Luteolin disturbs cell adhesion through alpha‐containing integrins and expression of modified LDL‐scavenging receptors required for foam cell formation

Abstract

The leukocyte recruitment and transmigration across the endothelial barrier into the vessel wall are crucial steps in promoting atherosclerosis. Oxidatively modified LDL (oxLDL) causally involved in the development of atherosclerosis has been shown to facilitate leukocyte transmigration. Our previous study showed that the flavone luteolin inhibited oxLDL‐triggered expression of cell adhesion molecules on vascular endothelial cells responsible for leukocyte recruitment. The present study examined whether luteolin blocked the monocyte‐endothelium interaction through monocyte integrin and inhibited the foam cell formation of THP‐1‐derived macrophages. We found that luteolin hampered the TNF‐α‐activated expression of THP‐1 monocyte integrin alpha. In addition, luteolin at non‐toxic doses mitigated the TNF‐α‐activated MMP‐9 secretion of THP‐1 monocytes. When THP‐1‐derived macrophages were treated with 10 µg/mL oxLDL or acetyl LDL, luteolin dampened expression of lectin‐like oxidized LDL receptor‐1 and SR‐A. These findings suggest that luteolin was effective in the disturbing TNF‐α‐activated cell adhesion through alpha‐containing integrins of monocytes and inhibiting modified LDL uptake through LDL‐scavenging receptors of macrophages. Therefore, dietary luteolin may be an anti‐atherogenic agent blocking the monocyte‐endothelium interactions. Supported by Brain Korea 21