Very low-density lipoprotein induces interleukin-1β 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-1β (IL-1β) in human peripheral blood monocyte-derived macrophages. IL-1β 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-1β, VLDL alone induced secretion of IL-1β from human monocyte-derived macrophages. This effect was suppressed by an inhibitor of caspase-1, the protease which cleaves pro-IL-1β. VLDL treatment activated caspase-1, as indicated by increased levels of the caspase-1 p20 subunit. Furthermore, VLDL increased IL-1β mRNA expression, which was associated with activation of transcription factor AP-1. Inhibition of caspase-1 did not influence IL-1β mRNA expression. In conclusion, VLDL induces IL-1β mRNA expression, caspase-1 activation, and IL-1β release from macrophages, suggesting that VLDL can promote inflammation in atherosclerotic lesions.