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

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 m...

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Autores principales: Matsuo, Koji, Yamamoto, Suguru, Wakamatsu, Takuya, Takahashi, Yoshimitsu, Kawamura, Kazuko, Kaneko, Yoshikatsu, Goto, Shin, Kazama, Junichiro J., Narita, Ichiei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549743/
https://www.ncbi.nlm.nih.gov/pubmed/26287243
http://dx.doi.org/10.3390/toxins7083155
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author Matsuo, Koji
Yamamoto, Suguru
Wakamatsu, Takuya
Takahashi, Yoshimitsu
Kawamura, Kazuko
Kaneko, Yoshikatsu
Goto, Shin
Kazama, Junichiro J.
Narita, Ichiei
author_facet Matsuo, Koji
Yamamoto, Suguru
Wakamatsu, Takuya
Takahashi, Yoshimitsu
Kawamura, Kazuko
Kaneko, Yoshikatsu
Goto, Shin
Kazama, Junichiro J.
Narita, Ichiei
author_sort Matsuo, Koji
collection PubMed
description 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.
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spelling pubmed-45497432015-08-31 Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate Matsuo, Koji Yamamoto, Suguru Wakamatsu, Takuya Takahashi, Yoshimitsu Kawamura, Kazuko Kaneko, Yoshikatsu Goto, Shin Kazama, Junichiro J. Narita, Ichiei Toxins (Basel) Article 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. MDPI 2015-08-14 /pmc/articles/PMC4549743/ /pubmed/26287243 http://dx.doi.org/10.3390/toxins7083155 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Matsuo, Koji
Yamamoto, Suguru
Wakamatsu, Takuya
Takahashi, Yoshimitsu
Kawamura, Kazuko
Kaneko, Yoshikatsu
Goto, Shin
Kazama, Junichiro J.
Narita, Ichiei
Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate
title Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate
title_full Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate
title_fullStr Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate
title_full_unstemmed Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate
title_short Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate
title_sort increased proinflammatory cytokine production and decreased cholesterol efflux due to downregulation of abcg1 in macrophages exposed to indoxyl sulfate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549743/
https://www.ncbi.nlm.nih.gov/pubmed/26287243
http://dx.doi.org/10.3390/toxins7083155
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