Oxidized lipoproteins including HDL and their lipid peroxidation products inhibit TNF-alpha secretion by THP-1 human macrophages.
It has been established that oxidized LDL (ox-LDL) modifies cytokine secretion by macrophages, for example, by reducing tumor necrosis factor alpha (TNF-(alpha) 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-HDL2, ox-HDL3) compared with that of ox-LDL and some products of oxidation (hydroperoxides and aldehydes) on the secretion of TNF-alpha from THP-1 human monocytes derived macrophages in vitro. HDL2, HDL3 and LDL were oxidized with 10 microM 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-alpha 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-alpha secretion measured after a further 22 h of incubation. An inhibition of TNF-alpha by ox-HDL2 (p < .05), ox-HDL3 (p < .05) and ox-LDL (p < .05) from THP-1 macrophages was observed in the presence and absence of LPS. This inhibition remained the same after incubation with ox-HDL 12 h and 24 h. Hydroperoxides of linoleic acid did not modify TNF-alpha secretion by cells while five out of eight aldehydes analyzed (2,4-heptadienal, hexanal, 2-nonenal, 2-octenal, 2,4-decadienal) inhibited TNF-alpha secretion (p < .05). These findings demonstrate that ox-HDL, and some of its lipid peroxidation products, plays a role in the modulation of the inflammatory response by macrophages as previously observed for ox-LDL.
Girona
J
J
Unitat de Recerca de Lipids i Arteriosclerosi, Unitat d'Investigació de l'Hospital Sant Joan, Facultat de Medicina, Universitat Rovira i Virgili, Sant Llorenç, Reus, Spain.
La Ville
A E
AE
Heras
M
M
Olivé
S
S
Masana
L
L
D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D010084:Oxidation-Reduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000447:Aldehydes; D008054:Lipid Peroxides; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D014409:Tumor Necrosis Factor-alpha