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

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-alpha (TNF)-alpha. The cellular source of obstruction induced renal TNF-alpha 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-alpha mRNA expression (reverse transcriptase polymerase chain reaction), TNF-alpha protein production (enzyme-linked immunosorbent assay), TNF-alpha cellular localization (immunohistochemistry) and leukocyte infiltration (leukocyte staining).

RESULTS:

Renal TNF-alpha 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-alpha production localized primarily to renal cortical tubular cells following obstruction and the time point of maximal TNF-alpha production (3 days of obstruction) were not associated with a significant renal inflammatory cell infiltrate.

CONCLUSIONS:

TNF-alpha 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-alpha expression during renal obstruction may have therapeutic implications for the targeted inhibition of TNF-alpha production and potential amelioration of obstructive renal injury.

• Authors: Rosalia Misseri, Daniel R Meldrum, Pierre Dagher, Karen Hile, Richard C Rink, Kirstan K Meldrum
• Journal: The Journal of urology (J Urol) Vol. 172 Issue 4 Pt 2 Pg. 1595-9; discussion 1599 (Oct 2004) ISSN: 0022-5347 [Print] United States
• PMID: 15371768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Necrosis Factor-alpha

Topics

• Animals
• Chemotaxis, Leukocyte
• Kidney Tubules (metabolism)
• Male
• Rats
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (biosynthesis)
• Ureteral Obstruction (immunology, metabolism)