Oxidized Lipoproteins Including HDL and Their Lipid Peroxidation Products Inhibit TNF-α Secretion by THP-1 Human Macrophages

Abstract It has been established that oxidized LDL (ox-LDL) modifies cytokine secretion by macrophages, for example, by reducing tumor necrosis factor alpha (TNF-( α ) m-RNA. However, little is known about the effects of oxidized high density lipoprotein (ox-HDL). This study reports the effects of ox-HDL subfractions 2 and 3 (ox-HDL 2 , ox-HDL 3 ) compared with that of ox-LDL and some products of oxidation (hydroperoxides and aldehydes) on the secretion of TNF- α from THP-1 human monocytes derived macrophages in vitro. HDL 2 , HDL 3 and LDL were oxidized with 10 μ M Cu ++ for 12 h and/or 24 h. Native and oxidized HDL and LDL were incubated for 24 h with macrophages with or without LPS (10 ng/ml) after which TNF- α secretion was measured in the culture medium. Lipid hydroperoxides and apolar aldehydes were also incubated with the cells for 2 h following which the medium was replaced and TNF- α secretion measured after a further 22 h of incubation. An inhibition of TNF- α by ox-HDL 2 ( p 3 ( p p α secretion by cells while five out of eight aldehydes analyzed (2,4-heptadienal, hexanal, 2-nonenal, 2-octenal, 2,4-decadienal) inhibited TNF- α secretion ( p