2,4-Decadienal downregulates TNF-alpha gene expression in THP-1 human macrophages

Oxidized lipoproteins inhibit TNF-alpha secretion by human THP-1 macrophage s due, at least in part, to aldehydes derived from the oxidation of polyuns aturated fatty acids. This study extends these findings by investigating th e effect of three aldehydes (2,4-decadienal (2,4-DDE), hexanal and 4-hydrox ynonenal (4-HNE)) on TNF-alpha and IL-1 beta mRNA expression. The 2,4-DDE a nd 4-HNE showed considerable biological activity which induced cytotoxicity on THP-1 macrophages at concentration of 50 muM. Hexanal, on the other han d, had a lower cytotoxic capacity and concentration of 1000 muM was needed for the effect to be observed. Exposure of THP-1 macrophages to aldehydes f or 24 h inhibited TNF-alpha mRNA expression but increased or did not affect IL-1 beta mRNA levels. The inhibitory action of 2,4-DDE was dose dependent and began at 5 muM (46%, P < 0.001). The effect of 4-HNE was less inhibito ry than 4-DDE but only when cytotoxic concentrations were used (50 muM). Ve ry high concentrations of hexanal (200 muM) were needed to inhibit TNF-alph a expression (23%, P < 0.001). This downregulation of TNF-alpha gene expres sion by 2,4-DDE was parallel to a lower protein production. These data indi cate that low levels of 2,4-DDE may modulate inflammatory action by inhibit ing TNF-alpha mRNA gene expression and that the biological activity of 2,4- DDE may be involved in the development of atherosclerosis. (C) 2001 Elsevie r Science Ireland Ltd. All rights reserved.