TNF-α mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling

R. Misseri, D. R. Meldrum, C. A. Dinarello, Pierre Dagher, K. L. Hile, R. C. Rink, K. K. Meldrum

Research output: Contribution to journalArticle

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Abstract

Obstruction of the upper urinary tract induces a progressive loss in renal mass through apoptotic renal cell death. Although TNF-α has been implicated in ischemia-reperfusion-induced apoptotic renal cell death, its role in obstructive renal cell apoptosis remains unknown. To study this, male Sprague-Dawley rats were subjected to left unilateral ureteral obstruction vs. sham operation. Twenty-four hours before surgery and every 84 h thereafter, rats received either vehicle or a pegylated form of soluble TNF receptor type 1 (PEG-sTNFR1). The kidneys were harvested 1, 3, or 7 days postoperatively, and tissue samples were subsequently analyzed for TNF-α (ELISA, RT-PCR), Fas ligand (RT-PCR), apoptosis (TUNEL, ELISA), and caspase 8 and 3 activity (Western blot). Renal obstruction induced increased tissue TNF-α and Fas ligand mRNA levels, TNF-α protein production, apoptotic renal tubular cell death, and elevated caspase 8 and 3 activity, whereas treatment with PEG-sTNFR1 significantly reduced obstruction-induced TNF-α production, renal tubular cell apoptosis, and caspase activity. PEG-sTNFR1 did not significantly alter Fas ligand expression. These results demonstrate that TNF-α mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling and identify TNF-α neutralization as a potential therapeutic option for the amelioration of obstruction-induced renal injury.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume288
Issue number2 57-2
DOIs
StatePublished - Feb 2005

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Apoptosis
Kidney
Fas Ligand Protein
Tumor Necrosis Factor Receptors
Cell Death
Caspase 8
Caspase 3
Enzyme-Linked Immunosorbent Assay
Ureteral Obstruction
Polymerase Chain Reaction
In Situ Nick-End Labeling
Caspases
Urinary Tract
Reperfusion
Sprague Dawley Rats
Ischemia
Western Blotting
Messenger RNA
Wounds and Injuries
Therapeutics

Keywords

  • Cytokine
  • Inflammation
  • Kidney
  • Tumor necrosis factor receptor 1

ASJC Scopus subject areas

  • Physiology

Cite this

TNF-α mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling. / Misseri, R.; Meldrum, D. R.; Dinarello, C. A.; Dagher, Pierre; Hile, K. L.; Rink, R. C.; Meldrum, K. K.

In: American Journal of Physiology - Renal Physiology, Vol. 288, No. 2 57-2, 02.2005.

Research output: Contribution to journalArticle

Misseri, R. ; Meldrum, D. R. ; Dinarello, C. A. ; Dagher, Pierre ; Hile, K. L. ; Rink, R. C. ; Meldrum, K. K. / TNF-α mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling. In: American Journal of Physiology - Renal Physiology. 2005 ; Vol. 288, No. 2 57-2.
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