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Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate

Authors :
Koji Matsuo
Suguru Yamamoto
Takuya Wakamatsu
Yoshimitsu Takahashi
Kazuko Kawamura
Yoshikatsu Kaneko
Shin Goto
Junichiro J. Kazama
Ichiei Narita
Source :
Toxins, Vol 7, Iss 8, Pp 3155-3166 (2015)
Publication Year :
2015
Publisher :
MDPI AG, 2015.

Abstract

One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1β, IS 1.0 mM: 101.8 ± 21.8 pg/mL vs. 0 mM: 7.0 ± 0.3 pg/mL, TNF-α, IS 1.0 mM: 96.6 ± 11.0 pg/mL vs. 0 mM: 15.1 ± 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% ± 7.3% vs. 0 mM: 43.5% ± 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD.

Details

Language :
English
ISSN :
20726651
Volume :
7
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Toxins
Publication Type :
Academic Journal
Accession number :
edsdoj.8cf4e1a5bfb24b8aaced9ea3ed3dbb58
Document Type :
article
Full Text :
https://doi.org/10.3390/toxins7083155