Interplay between Liver X Receptor and Hypoxia Inducible Factor 1α Potentiates Interleukin-1β Production in Human Macrophages

Cell Reports

卷:31

Jean Baptiste Julla¹  Louise Basmaciyan²  Mano Joseph Mathew²  Antoine Jalil²  Valentin Crespy²  Eric Steinmetz³  Wilfried Le Goff⁴  Charles Thomas⁴  Aline Laubriet⁴  David Masson⁴  Adam Ceroi⁴  Philippe Saas⁵  Cédric Rébé⁶  Nicolas Venteclef⁷  Jean-Paul Pais de Barros⁸  Louise Ménégaut⁹  Laurent Lagrost⁹  Charlène Magnani⁹  Valentin Dérangère⁹  Adélie Dumont⁹ 

[1] CHRU Dijon Bourgogne, Laboratory of Clinical Chemistry, 21000 Dijon, France;

[2] FCS Bourgogne-Franche Comté, LipSTIC LabEx, 21000 Dijon, France;

[3] FCS Bourgogne-Franche Comté, LipSTIC LabEx, 25000 Besançon, France;

[4] INSERM, LNC UMR1231, 21000 Dijon, France;

[5] Parasitology-Mycology Department, University Hospital of Dijon, 21000 Dijon, France;

[6] Centre de Recherche des Cordeliers, INSERM, Université de Paris, IMMEDIAB Laboratory, 75006 Paris, France;

[7] UMR A PAM, Équipe Vin, Aliment, Microbiologie, Stress, Université Bourgogne Franche-Comté, AgroSup Dijon, 21078 Dijon Cedex, France;

[8] Université Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, INSERM, UMR1098, 25000 Besançon, France;

[9] Université Bourgogne Franche-Comté, LNC UMR1231, 21000 Dijon, France;

关键词: liver X receptors;    interleukin-1 beta;    hypoxia inducible factor 1 alpha;    macrophages;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Low-grade inflammation is constitutive of atherosclerosis, and anti-inflammatory therapy inhibiting interleukin-1β (IL-1β) reduces the rate of cardiovascular events. While cholesterol accumulation in atheroma plaque and macrophages is a major driver of the inflammatory process, the role of the LXR cholesterol sensors remains to be clarified. Murine and human macrophages were treated with LXR agonists for 48 h before Toll-like receptor (TLR) stimulation. Unexpectedly, we observe that, among other cytokines, LXR agonists selectively increase IL1B mRNA levels independently of TLR activation. This effect, restricted to human macrophages, is mediated by activation of HIF-1α through LXR. Accordingly, LXR agonists also potentiate other HIF-1α-dependent pathways, such as glycolysis. Treatment of human macrophages with carotid plaque homogenates also leads to induction of IL1B in an LXR-dependent manner. Thus, our work discloses a mechanism by which cholesterol and oxysterols trigger inflammation in atherosclerosis. This suggests perspectives to target IL-1β production in atherosclerotic patients.

【 授权许可】

Unknown