Electronegative LDL induces priming and inflammasome activation leading to IL-1β release in human monocytes and macrophages

Biochimica Et Biophysica Acta
Montserrat EstruchJordi Ordonez-Llanos

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

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Citations

May 29, 2016·Biochimica Et Biophysica Acta·Montserrat EstruchSonia Benitez
Oct 14, 2017·The Journal of Clinical Endocrinology and Metabolism·Liang-Yin KeShyi-Jang Shin
Mar 31, 2018·Current Medicinal Chemistry·Andrea Rivas-UrbinaJosé Luis Sánchez-Quesada
Nov 20, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Tzu-Ching YangShao-Chun Lu
Sep 20, 2019·Mediators of Inflammation·Po-Yuan ChangShao-Chun Lu
Dec 21, 2019·Inflammation·Gustavo Luis TripodiDulcineia Saes Parra Abdalla
Jan 13, 2019·The Journal of Biological Chemistry·Andrzej WitkowskiGiorgio Cavigiolio

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