2,4-Decadienal downregulates TNF-alpha gene expression in THP-1 human macrophages.
Oxidized lipoproteins inhibit TNF-alpha secretion by human THP-1 macrophages due, at least in part, to aldehydes derived from the oxidation of polyunsaturated fatty acids. This study extends these findings by investigating the effect of three aldehydes (2,4-decadienal (2,4-DDE), hexanal and 4-hydroxynonenal (4-HNE)) on TNF-alpha and IL-1beta mRNA expression. The 2,4-DDE and 4-HNE showed considerable biological activity which induced cytotoxicity on THP-1 macrophages at concentration of 50 microM. Hexanal, on the other hand, had a lower cytotoxic capacity and concentration of 1000 microM was needed for the effect to be observed. Exposure of THP-1 macrophages to aldehydes for 24 h inhibited TNF-alpha mRNA expression but increased or did not affect IL-1beta mRNA levels. The inhibitory action of 2,4-DDE was dose dependent and began at 5 microM (46%, P<0.001). The effect of 4-HNE was less inhibitory than 4-DDE but only when cytotoxic concentrations were used (50 microM). Very high concentrations of hexanal (200 microM) were needed to inhibit TNF-alpha expression (23%, P<0.001). This downregulation of TNF-alpha gene expression by 2,4-DDE was parallel to a lower protein production. These data indicate that low levels of 2,4-DDE may modulate inflammatory action by inhibiting TNF-alpha mRNA gene expression and that the biological activity of 2,4-DDE may be involved in the development of atherosclerosis.
Girona
J
J
Unitat de Recerca de Lípids i Arteriosclerosi, Facultat de Medicina, Universitat Rovira i Virgili, C/Sant Llorenç 21, 43201 Reus, Spain.
Vallvé
J C
JC
Ribalta
J
J
Heras
M
M
Olivé
S
S
Masana
L
L
D000447:Aldehydes / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D000447:Aldehydes; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C057349:2,4-decadienal; C010463:n-hexanal; C027576:4-hydroxy-2-nonenal