BPB Reports

Paper Details

BPB Reports
Vol. 4 No. 6 p.198-201 2021
Report
Indoxyl Sulfate Induces an Inflammatory Response in the Proximal Tubule via Macrophages
  • Kazuma Higashisaka (Graduate School of Pharmaceutical Sciences, Osaka University / Institute for Advanced Co-Creation Studies, Osaka University / higashisaka@phs.osaka-u.ac.jp)
  • Yasuo Tsutsumi (Graduate School of Pharmaceutical Sciences, Osaka University / Global Center for Medical Engineering and Informatics, Osaka University / ytsutsumi@phs.osaka-u.ac.jp)
Ryo Isaka 1) , Nanan Ishida 1) , Go Kitahara 1) , Yuji Sakahashi 1) , Yuya Haga 1) , Hirofumi Tsujino 1) 2) , Kazuya Nagano 1) 3) , Kazuma Higashisaka 1) 4) , Yasuo Tsutsumi 1) 5)
1) Graduate School of Pharmaceutical Sciences, Osaka University , 2) The Museum of Osaka University , 3) School of Pharmaceutical Sciences, Wakayama Medical University , 4) Institute for Advanced Co-Creation Studies, Osaka University , 5) Global Center for Medical Engineering and Informatics, Osaka University
Received: October 11, 2021;   Accepted: November 30, 2021;   Released: December 09, 2021
Keywords: indoxyl sulfate, inflammation, macrophage, proximal tubule
Abstracts

Indoxyl sulfate is a uremic toxin and is difficult to remove by hemodialysis owing to its tight binding to albumin in the blood. There is therefore concern that it could cause inflammatory responses in renal tissue, leading to worsening of renal failure. Recent reports suggest that indoxyl sulfate not only directly affects renal cells but also induces an inflammatory response via macrophages infiltrating renal tissues. However, the mechanism of the indoxyl-sulfate-induced inflammatory response mediated by macrophages and the effect of macrophages on renal cells have not yet been elucidated. Here, we evaluated the effect of indoxyl sulfate on the inflammatory response of macrophages and the effect of macrophages on renal cells. Indoxyl sulfate upregulated the expression of tumor necrosis factor-α (TNF-α) by THP-1 macrophages. Moreover, it activated the transcriptional regulator nuclear factor-kappa B (NF-κB) p65, and an inhibitor of NF-κB suppressed indoxyl-sulfate-induced TNF-α elevation. Supernatant of THP-1 macrophages treated with indoxyl sulfate increased the mRNA expression levels of inflammatory cytokines in HK-2 renal proximal tubular epithelial cells. These results suggest that indoxyl sulfate increases TNF-α expression through the activation of NF-κB in THP-1 macrophages and that macrophages stimulated with indoxyl sulfate induce an inflammatory response in the proximal tubular epithelial cells.