Interleukin-1β Regulates PCSK9 and LDL Receptor Expression together with de novo Cholesterol Synthesis in HepG2 Cells

Abstract

Background and Aim : Chronic inflammation is associated with changes in lipid and cholesterol metabolism in the liver. A predominant finding is changes in surface LDL receptor (LDLR) expression at various stages of disease which may be associated with serum increases in LDL and therefore increased risk of developing atherosclerosis. At the same time, increased cholesterol accumulation has also been observed and linked to development of fatty liver. Methods : Here, we use the hepatoma cell line HepG2 as a model of highly active chronic inflammation and report on cytokine mediated changes in expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), LDLR and low density lipoprotein receptor-related protein 1 (LRP-1) as well as expression of rate limiting enzymes in the cholesterol synthesis. Results : Overall, we observed a predominant role of Interleukin-1b (IL-1b) in reduction of PCSK9 accompanied by increased LDLR expression, whereas LRP-1 expression was not influenced. Key enzymes in cholesterol biosynthesis were all downregulated by IL-1b. Conclusion : In conclusion, we identify IL-1b as a key regulator of cholesterol metabolism.