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


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.
Misseri
Rosalia
R
Department of Urology, Indiana University, Indianapolis, Indiana, USA.
Meldrum
Daniel R
DR
Dagher
Pierre
P
Hile
Karen
K
Rink
Richard C
RC
Meldrum
Kirstan K
KK
D000818:Animals; D002634:Chemotaxis, Leukocyte; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014517:Ureteral Obstruction / Q000276:immunology / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha