NF-κB-inducing kinase increases renal tubule epithelial inflammation associated with diabetes

Ronald Tilton, Yanhua Zhao, Srijita Banerjee, Wanda S. Lejeune, Sanjeev Choudhary

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The impact of increased NF-κB-inducing kinase (NIK), a key component of the NF-κB activation pathways, on diabetes-induced renal inflammation remains unknown. We overexpressed NIK wild type (NIKwt) or kinase-dead dominant negative mutants (NIKdn) in HK-2 cells and demonstrated that RelB and p52, but not RelA, abundance and DNA binding increased in nuclei of NIKwt but not NIKdn overexpressed cells, and this corresponded with increases in multiple proinflammatory cytokines. Since TRAF3 negatively regulates NIK expression, we silenced TRAF3 by 50; this increased nuclear levels of p52 and RelB, and transcript levels of proinflammatory cytokines and transcription factors. In HK-2 cells and mouse primary proximal tubule epithelial cells treated with methylglyoxal-modified albumin, multiple proinflammatory cytokines and NIK were increased in association with increased nuclear RelB and p52. These observations indicate that NIK regulates proinflammatory responses of renal proximal tubular epithelial cells via mechanisms involving TRAF3 and suggest a role for NF-κB noncanonical pathway activation in modulating diabetes-induced inflammation in renal tubular epithelium.

Original languageEnglish (US)
Article number192564
JournalExperimental Diabetes Research
Volume2011
DOIs
StatePublished - 2011

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Phosphotransferases
TNF Receptor-Associated Factor 3
Inflammation
Kidney
Cytokines
Epithelial Cells
Pyruvaldehyde
Cells
Diabetes
Albumins
Transcription Factors
Epithelium
DNA
Activation
Proximal
Pathway

ASJC Scopus subject areas

  • Medicine(all)
  • Endocrinology, Diabetes and Metabolism
  • Music

Cite this

NF-κB-inducing kinase increases renal tubule epithelial inflammation associated with diabetes. / Tilton, Ronald; Zhao, Yanhua; Banerjee, Srijita; Lejeune, Wanda S.; Choudhary, Sanjeev.

In: Experimental Diabetes Research, Vol. 2011, 192564, 2011.

Research output: Contribution to journalArticle

Tilton, Ronald ; Zhao, Yanhua ; Banerjee, Srijita ; Lejeune, Wanda S. ; Choudhary, Sanjeev. / NF-κB-inducing kinase increases renal tubule epithelial inflammation associated with diabetes. In: Experimental Diabetes Research. 2011 ; Vol. 2011.
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