IL-6R (trans-signaling) is a key regulator of reverse cholesterol transport in lipid-laden macrophages.

Autor: Al-Rashed F; Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, Dasman, Kuwait, PO BOX 1180, Dasman 15462, Kuwait. Electronic address: fatema.alrashed@dasmaninstitute.org., AlSaeed H; Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, Dasman, Kuwait, PO BOX 1180, Dasman 15462, Kuwait., Almansour N; Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, Dasman, Kuwait, PO BOX 1180, Dasman 15462, Kuwait., Al-Mulla F; Genetics and Bioinformatics Department, Dasman Diabetes Institute, Kuwait, Kuwait., Hannun YA; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA., Ahmad R; Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, Dasman, Kuwait, PO BOX 1180, Dasman 15462, Kuwait.
Jazyk: angličtina
Zdroj: Clinical immunology (Orlando, Fla.) [Clin Immunol] 2024 Oct; Vol. 267, pp. 110351. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1016/j.clim.2024.110351
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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