IL-1β and TNF-α suppress apolipoprotein (APO) E secretion and APO A-I expression in HepG2 cells

The effect of cytokines on apolipoprotein E (ape E) production and secretion was investigated in a human hepatoma cell line HepG2. Incubation of HepG2 cells with interleukin 1β (IL-1β) or tumour necrosis factor α (TNF-α) for 48 h resulted in a significant dose-related decrease of apo E concentration in the culture medium, while intracellular apo E content increased without change in mRNA level. In contrast, IL-1β and TNF-α decreased both intracellular and medium apo A-I. Elution profiles of cholesterol and apolipoproteins revealed that apo E was present in apo E-rich high density lipoprotein (HDL) fraction and apo A-I was in apo E-rich HDL and small HDL fractions. IL-1β and TNF-α decreased both apo E and apo A-I in these fractions. The present results suggest that IL-1β and TNF-α suppress hepatic apo A-I expression and secretion but not expression of apo E, which could contribute to the abnormal lipid metabolism in certain cytokine-mediated inflammatory diseases.