Unilateral ureteral obstruction induces renal tubular cell production of tumor necrosis factor-α independent of inflammatory cell infiltration

Rosalia Misseri, Daniel R. Meldrum, Pierre Dagher, Karen Hile, Richard C. Rink, Kirstan K. Meldrum, Nicola Cappozza

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Purpose: Obstructive uropathy is a significant clinical problem that results in apoptotic renal cell death and progressive renal fibrosis. A number of different inflammatory mediators have been implicated in the pathophysiology of obstruction induced renal injury including tumor necrosis factor-α (TNF)-α. The cellular source of obstruction induced renal TNF-α production and its relationship to renal inflammatory cell infiltration remain unknown. Materials and Methods: Male Sprague-Dawley rats were anesthetized and exposed to varying lengths of unilateral ureteral obstruction vs sham operation. The kidneys were harvested following renal injury and evaluated for TNF-α mRNA expression (reverse transcriptase polymerase chain reaction), TNF-α protein production (enzyme-linked immunosorbent assay), TNF-α cellular localization (immunohistochemistry) and leukocyte infiltration (leukocyte staining). Results: Renal TNF-α mRNA expression and protein production peaked following 3 days of ureteral obstruction (54 ± 5% vs sham 22 ± 9% of glyceraldehyde-3-phosphate dehydrogenase mRNA, p <0.05 and 204 ± 13 vs sham 84 ± 9 pg/ml, p <0.05, respectively). TNF-α production localized primarily to renal cortical tubular cells following obstruction and the time point of maximal TNF-α production (3 days of obstruction) were not associated with a significant renal inflammatory cell infiltrate. Conclusions: TNF-α is produced by the renal cortical tubular cells in response to ureteral obstruction and independent of a significant inflammatory cell infiltrate. Identification of the cellular source of TNF-α expression during renal obstruction may have therapeutic implications for the targeted inhibition of TNF-α production and potential amelioration of obstructive renal injury.

Original languageEnglish (US)
Pages (from-to)1595-1599
Number of pages5
JournalJournal of Urology
Volume172
Issue number4 II
DOIs
StatePublished - Oct 2004

Keywords

  • Cytokines
  • Inflammation
  • Kidney
  • Leukocytes

ASJC Scopus subject areas

  • Urology

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