Inflammatory response and insulin signaling alteration induced by PCB77

摘要

A specific mechanism whereby inflammation may contribute to cardiovascular diseases (CVD), insulin resistance (IR) and type II diabetes is the induction of endothelial dysfunction placing the vascular endothelium in a key unifying position for the shared pathogenesis of these diseases. However, the mechanisms by which PCBs induce endothelial cell dysfunction are not clearly understood. In the present study, we used human umbilical vascular endothelial cells (HUVEC) as model, and inflammatory response and insulin signaling alteration induced by PCBs were examined. Results showed that PCB77 induced the expression of proinflammatory cytokines including IL-6 and TNFα and induced U937 adhesion to HUVEC cells consistent with increased NFκB transcription activity. On the other hand, PCB77 blocked insulin-activated Akt signaling pathway, which was restored by pretreatment with TNFα neutralization antibody. In conclusion, PCB77 showed the potential to induce the expression of proinflammatory cytokines including IL-6, which has been shown to be powerful independent risk predictor of CVD. And PCB77 was observed to alter insulin-activated Akt signaling by TNFα secretion for the first time.