Serum retinol-binding protein-induced endothelial inflammation is mediated through the activation of toll-like receptor 4

“Retinol-binding protein 4 (RBP4) is a novel adipokine (adipose-derived cytokine) that is clinically associated with obesity, insulin resistance, type 2 diabetes (T2DM), and cardiovascular disease. In addition, patients with proliferative diabetic retinopathy (DR) have increased serum RBP4 levels compared to diabetic patients with mild or no retinopathy, which raises the possibility that RBP4 is somehow involved in the pathogenesis of DR. We demonstrated previously that RBP4 elevation induces inflammation in primary human retinal microvascular endothelial cells (HRECs) and human umbilical vein endothelial cells (HUVECs) by increasing the expression of proinflammatory cytokines, chemokines, and adhesion molecules, including interleukin 6 (IL-6), monocyte chemoattractant protein (MCP-1), endothelial cell selectin (E-selectin), vascular cell adhesion molecule 1 (VCAM-1), and intracellular adhesion molecule 1 (ICAM-1). We have also shown that RBP4-induced endothelial inflammation is retinol independent and involves activation of nuclear factor κB (NF-κB). In the present study, we used HRECs as a model system to learn more about the cell receptor and signaling pathways that modulate the proinflammatory activity of RBP4.”

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