Polychlorinated biphenyls (
PCBs) are organic
environmental pollutants that are accused of various toxic effects. PCB exposure is widely believed to be associated with
atherosclerosis, but the underlying mechanisms are unclear. Although
PCBs are easily metabolized, there is rarely information on the effects of their metabolites on
atherosclerosis. Currently, we evaluate the effect of 2,3,5-trichloro-6-phenyl-[1,4]-
benzoquinone (PCB29-pQ) on the critical phase of
atherosclerosis development, that is, the formation of macrophage-derived foam cells. We exposed
Ox-LDL-induced RAW264.7 cells to 2.5 μM and 5 μM
PCB29-pQ. Varieties of evidence have demonstrated that
PCB29-pQ promotes foam cell formation and develops proinflammatory cascade and cell necroptosis. In detail, we observed that
PCB29-pQ increased levels of total
cholesterol (TC), free
cholesterol (FC),
triglyceride (TG), and
cholesteryl ester (CE) by increasing the
cholesterol influx and reducing the
cholesterol efflux. Moreover, we found that
PCB29-pQ induced inflammatory
cytokines, such as
tumor necrosis factor (TNF-α),
interleukin 6 (IL-6), and IL-1β, released by activating the
mitogen-activated protein kinase (MAPK)-
nuclear factor kappa B (NF-κB) inflammatory pathway. In addition, we demonstrated that
PCB29-pQ induced cell necroptosis via receptor interacting
protein kinases 1 and 3 (RIPK1/3) and a mixed-lineage
kinase domain-like (MLKL) pathway. Finally, the overproduction of
reactive oxygen species (ROS) by
PCB29-pQ played significant roles in these processes, which could be reversed with an
antioxidant. Overall, our results indicated that
PCB29-pQ promoted the macrophage formation of foam cells,
inflammation, and cell necroptosis.