IL-6R (trans-signaling) is a key regulator of reverse cholesterol transport in lipid-laden macrophages
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 267(2024) vom: 30. Sept., Seite 110351 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
|
| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article ABCA1 Atherosclerosis Cholesterol Cytokines IL-6 LDLR Monocytes gp130 97C5T2UQ7J mehr... |
| Zusammenfassung: | Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. Atherosclerosis is a cardiovascular disease caused by cholesterol-laden arterial plaques. This study evaluated the correlation between interleukin-6 (IL-6), its receptors (IL6R/CD126), and glycoprotein 130 (gp130) alongside atherosclerosis biomarkers in a cohort of 142 subjects, equally divided between lean and obese individuals. Subsequent analyses used THP-1-derived macrophages to assess the biochemical impact of inhibiting IL-6 receptors. IL-6 secretion increased with atherosclerosis in obese subjects, while IL6R/CD126 and gp130 on monocytes decreased. Pharmacological gp130 inhibition altered lipid metabolism, increasing LDLR gene expression and cholesterol synthesis via SREBF2 and mevalonate kinase, along with HMG-CoA reductase at protein levels. gp130-deficient cells produced more cholesterol and had lower ABCA1 levels, suggesting hindered cholesterol efflux. Filipin III staining confirmed cholesterol retention in gp130-inhibited cells. Ex-vivo investigation on lean PBMCs further defined the impact of gp130 inhibition on the reduction of cholesterol efflux. Our results indicates gp130 is crucial for macrophage reverse cholesterol transport and may be a target for atherosclerosis treatments |
|---|---|
| Beschreibung: | Date Completed 14.09.2024 Date Revised 24.09.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2024.110351 |