Native LDL potentiate TNFα and IL-8 production by human mononuclear cells

Activation of TLR2 and TLR4 by minimally modified low-density lipoprotein in human macrophages and monocytes triggers the inflammatory response

“…Our results show that stimulation with nLDL does not result in upregulation of TLR2 and TLR4 expression and does not induce TNF-␣ secretion in monocytes or macrophages, indicating that nLDL is an inactive molecule. Similarly, previous reports have shown that nLDL does not induce the secretion of pro-inflammatory cytokines [29]. In contrast, we observed that, similar to other endogenous antigens that are associated with a pro-inflammatory response [30,31], mmLDL induced upregulation of TLR2 and TLR4 and increased secretion of TNF-␣ in monocytes and macrophages.…”

Native LDL-Cholesterol Mediated Monocyte Adhesion Molecule Overexpression is Blocked by Simvastatin

“…It has been shown that modified forms of LDL are able to activate immune processes by stimulating monocyte migration and expression of adhesion molecules [27,28]. However, in the last few years it has become apparent that non-modified nLDL also has immune-stimulating properties, such as augmentation of adhesion molecule expression on vascular endothelial cells and cytokine production in monocytes [29,30]. In line with these studies, our investigation provides new information regarding the capacity of nLDL to potentiate monocyte adhesiveness and the role of simvastatin in inhibiting these processes.…”

Molecular Biology of Atherosclerosis

“…This upregulation was thought to be due to uptake of LDL through the LDL receptor and may have been due to an increase in membrane cholesterol. Subsequent studies suggest calcium transients may be involved in this activation with sensitization of monocytes so that they have increased production TNF-␣ and IL-8 when subsequently exposed to LPS (1293). Native LDL similarly caused calcium transients in endothelial cells with increased VCAM-1 and E-selectin expression (53).…”