Very low-density lipoprotein induces interleukin-1beta expression in macrophages.
Elevated plasma level of very low-density lipoprotein (VLDL) is a risk factor for coronary heart disease. We investigated the effect of VLDL on expression of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in human peripheral blood monocyte-derived macrophages. IL-1beta mRNA and protein expression was analysed by PCR and ELISA, respectively. Caspase activation was assessed by immunoblotting. Apart from potentiating lipopolysaccharide-induced secretion of IL-1beta, VLDL alone induced secretion of IL-1beta from human monocyte-derived macrophages. This effect was suppressed by an inhibitor of caspase-1, the protease which cleaves pro-IL-1beta. VLDL treatment activated caspase-1, as indicated by increased levels of the caspase-1 p20 subunit. Furthermore, VLDL increased IL-1beta mRNA expression, which was associated with activation of transcription factor AP-1. Inhibition of caspase-1 did not influence IL-1beta mRNA expression. In conclusion, VLDL induces IL-1beta mRNA expression, caspase-1 activation, and IL-1beta release from macrophages, suggesting that VLDL can promote inflammation in atherosclerotic lesions.
Stollenwerk
Maria M
MM
Department of Clinical Sciences, Lund University, Sweden. maria.stollenwerk@med.lu.se
Lindholm
Marie W
MW
Pörn-Ares
M Isabella
MI
Larsson
Anna
A
Nilsson
Jan
J
Ares
Mikko P S
MP
D001161:Arteriosclerosis / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D004247:DNA; D020169:Caspases; D020170:Caspase 1; D010100:Oxygen