Albiflorin inhibits the formation of THP-1-derived foam cells through the LOX-1/NF- κB pathway.
Ключови думи
Резюме
BACKGROUND
Foam cells are characteristic pathologic cells of atherosclerosis (AS), they are lipid-loaded macrophages present on atherosclerotic lesions. A large number of studies have shown that the pathogenesis of AS is the result of interactions between the lipid metabolism disorders and chronic inflammatory responses in the body. Albiflorin can inhibit the inflammatory response and it has shown a therapeutic effect on certain inflammatory diseases.
METHODS
In this study, a human acute monocytic leukemia cell line (THP-1)-derived foam cell model was established via oxidized low-density lipoprotein (ox-LDL) to observe the effects of albiflorin on the AS-characteristic foam cells.
RESULTS
Our results showed that, after the treatment with ox-LDL, macrophages induced by propylene glycol methyl ether acetate (PMA), presented large amounts of lipid deposition in their cytoplasm, indicating that the THP-1-derived foam cell model was successfully established. On the other hand, the same cells pretreated with albiflorin presented significantly reduced amounts of lipid deposition, and their contents of total cholesterol (TC) and triglyceride (TG) were also clearly lower. Besides, the expression levels of low-density lipoprotein receptor-1 (LOX-1) and nuclear factor-κB (NF-κB) were significantly decreased, and the expression levels of downstream factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also obviously decreased in the cells treated with albiflorin but not in the negative control cells. Moreover, after treatment of macrophages with different concentrations of ox-LDL, the expression levels of LOX-1 and NF-κB were up-regulated in an ox-LDL concentration-dependent manner, and so were the expression levels of IL-6 and TNF-α. And, it was found after treatment with LOX-1 neutralizing antibody or NF-κB inhibitor (during the foam cell formation induction via ox-LDL) that the lipid deposition in the cytoplasm of the cells was reduced, as in the cells treated with albiflorin.
CONCLUSIONS
Taken together, our findings suggest that albiflorin decreases lipid deposition in the cytoplasm and blocks the foaming process by regulating the LOX-1/NF-κB signaling pathway.
