Next Article in Journal
Anthrax Toxins in Context of Bacillus anthracis Spores and Spore Germination
Previous Article in Journal
Botulinum Toxin for Neuropathic Pain: A Review of the Literature
Article Menu

Export Article

Open AccessArticle
Toxins 2015, 7(8), 3155-3166; doi:10.3390/toxins7083155

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

1
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
2
Division of Blood Purification Therapy, Niigata University Medical and Dental Hospital, Niigata 951-8520, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: R. Vanholder
Received: 6 July 2015 / Revised: 31 July 2015 / Accepted: 6 August 2015 / Published: 14 August 2015
View Full-Text   |   Download PDF [708 KB, uploaded 14 August 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. View Full-Text
Keywords: indoxyl sulfate; macrophage; chronic kidney disease; atherosclerosis indoxyl sulfate; macrophage; chronic kidney disease; atherosclerosis
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Matsuo, K.; Yamamoto, S.; Wakamatsu, T.; Takahashi, Y.; Kawamura, K.; Kaneko, Y.; Goto, S.; Kazama, J.J.; Narita, I. Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate. Toxins 2015, 7, 3155-3166.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top