p-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene expressions in cultured proximal renal tubular cells

Nephrol Dial Transplant. 2013 Jan;28(1):70-8. doi: 10.1093/ndt/gfs133. Epub 2012 May 18.


Background: p-Cresol sulfate (PCS) and indoxyl sulfate (IS) have important roles in the kidney injury. The aim of this study was to determine the inflammatory response to PCS and IS.

Methods: Cultured mouse proximal renal tubular cells were treated with PCS or IS and analyzed by polymerase chain reaction array with an inflammation and immune panel. Gene annotation enrichment and functional annotation clustering were analyzed with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Functional networks of the target genes were analyzed with the algorithm GeneMANIA.

Results: PCS and IS increased the expression of inflammation associated genes. Sixteen upregulated gene clusters of cells treated with PCS or IS were found. The major cytokines in the functional networks generated by PCS or IS treatment were Tgfb1, Fasl, Il6/15, Il15, Csf1/3 and Cxcl10. The major intracellular signal triggered by PCS or IS included Stats, Smads, Nfkb2, Ikbkb, Bcl2 and Bax. In both PCS- and IS-treated cells, Col4a5, Cxc10, Fasl, Stat1 and Ikbkb were the target genes in the predicted molecular functional networks connected to Tgfb1.

Conclusions: PCS and IS stimulate significant cellular inflammation. Similar immune and cellular inflammatory responses were induced by PCS or IS on cultured proximal renal tubular cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cresols / pharmacology*
  • Gene Expression / drug effects*
  • Indican / pharmacology*
  • Inflammation / chemically induced*
  • Inflammation / genetics
  • Kidney / cytology*
  • Kidney / metabolism
  • Kidney Tubules, Proximal / cytology*
  • Kidney Tubules, Proximal / metabolism
  • Mice
  • Real-Time Polymerase Chain Reaction
  • Sulfuric Acid Esters / pharmacology*


  • Cresols
  • Sulfuric Acid Esters
  • 4-cresol sulfate
  • Indican