Electronegative LDL induces priming and inflammasome activation leading to IL-1β release in human monocytes and macrophages
Abstract
Electronegative LDL (LDL(−)), a modified LDL fraction found in blood, induces the release of inflammatory mediators in endothelial cells and leukocytes. However, the inflammatory pathways activated by LDL(−) have not been fully defined. We aim to study whether LDL(−) induced release of the first-wave proinflammatory IL-1β in monocytes and monocyte-derived macrophages (MDM) and the mechanisms involved. LDL(−) was isolated from total LDL by anion exchange chromatography. Monocytes and MDM were isolated from healthy donors and stimulated with LDL(+) and LDL(−) (100 mg apoB/L). In monocytes, LDL(−) promoted IL-1β release in a time-dependent manner, obtaining at 20 h-incubation the double of IL-1β release induced by LDL(−) than by native LDL. LDL(−)-induced IL-1β release involved activation of the CD14-TLR4 receptor complex. LDL(−) induced priming, the first step of IL-1β release, since it increased the transcription of pro-IL-1β (8-fold) and NLRP3 (3-fold) compared to native LDL. Several findings show that LDL(−) induced inflammasome activation, the second step necessary for IL-1β release. Preincubation of monocytes with K+ channel inhibitors decreased LDL(−)-induced IL-1β release. LDL(−) induced formation of the NLRP3-ASC complex....Continue Reading
References
Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome.
Citations
Related Concepts
Related Feeds
ApoE, Lipids & Cholesterol
Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.