PCB77‐induced adhesion molecule expression in primary endothelial cells is mediated through caveolae signaling

Abstract

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that can activate endothelial cells thus leading to atherogenic events. Induction of vascular adhesion molecules is a common feature in inflammatory environments, leading to the early development of atherosclerosis. We have investigated PCB77‐induced up‐regulation of adhesion molecules through caveolae‐regulated signaling in primary mouse aortic endothelial cells (MAECs) and porcine pulmonary artery endothelial cells (PAECs). PCB77 significantly increased the expression of vascular cell adhesion molecule‐1 (VCAM‐1) and intracellular adhesion molecule‐1 (ICAM‐1) measured by both Western blot and RT‐PCR in a dose dependent manner in both MAECs and PAECs. In addition, the adhesion of monocytes to PCB77‐activated endothelial cells was increased in a dose‐dependent pattern. Phosphorylation studies of caveolin‐1 and related kinases were conducted in endothelial cells containing either functional or siRNA silenced caveolin‐1 protein. Activation of these caveolae‐associated signaling pathways was decreased in absence of functional caveolae. These data provide the evidence that caveolae may play a critical role in regulating vascular endothelial cell activation and toxicity induced by persistent environmental pollutants such as coplanar PCBs. (Supported by grants from NIH/NIEHS (P42ES07380), the University of Kentucky AES and KRF‐2007‐357‐F00045)