Interplay between Liver X Receptor and Hypoxia Inducible Factor 1a Potentiates Interleukin-1b Production in Human Macrophages - Sorbonne Université
Article Dans Une Revue Cell Reports Année : 2020

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

Mano Joseph Mathew
Aline Laubriet
  • Fonction : Auteur
Valentin Crespy
  • Fonction : Auteur
Eric Steinmetz
  • Fonction : Auteur

Résumé

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.
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Dates et versions

hal-02967931 , version 1 (15-10-2020)

Identifiants

Citer

Louise Ménégaut, Charles Thomas, Antoine Jalil, Jean Baptiste Julla, Charlène Magnani, et al.. Interplay between Liver X Receptor and Hypoxia Inducible Factor 1a Potentiates Interleukin-1b Production in Human Macrophages. Cell Reports, 2020, 31 (7), pp.107665. ⟨10.1016/j.celrep.2020.107665⟩. ⟨hal-02967931⟩
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