The expression of mRNA for tumour necrosis factor‐α increases in the obstructed kidney of rats soon after unilateral ureteral ligation

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Summary: Cytokines, including transforming growth factor (TGF)‐β1, contribute to the tubulointerstitial fibrosis of ureteral obstruction. Tumour necrosis factor (TNF)‐α, a proinflammatory cytokine produced by multiple cells including macrophages and resident renal cells, has a role in inflammatory cell recruitment in glomerular injury. We measured TNF‐α mRNA in the renal cortex of rats at different times after the onset of unilateral ureteral obstruction (UUO) and determined whether angiotensin II (AngII) inhibition or total body irradiation affects the mRNA levels of TNF‐α. Rats were killed at 1, 2, 4, 24, 72 and 120h after UUO. Levels of TNF‐α mRNA increased significantly in the obstructed kidney at 1h (X 2), 2h (X 2.7), 4h (X 3.6), 24h (X 2.7), 72h (X 1.8) and 120h (X 2.8) after ureteral ligation when compared to the contralateral kidney of the same animals or to control (normal) kidneys. Tumour necrosis factor‐α mRNA increased in renal cortical tubules but not in glomeruli. Treatment with enalapril, an angiotensin‐converting enzyme (ACE) inhibitor, before and after UUO decreased TNF‐α mRNA levels in the obstructed kidney by about 40% at 4h after the onset of UUO, but at 120h there was no difference in TNF‐α levels in the obstructed kidney of treated and untreated animals. Total body irradiation, which depletes macrophages in the obstructed kidney, did not prevent the upregulation of TNF‐α mRNA expression at 4 h after UUO. Thus, TNF‐α may have a role in initiating tubulointerstitial injury in the obstructed kidney. Leucocytes infiltrating the renal interstitium of the obstructed kidney do not appear to contribute to the increased mRNA expression of TNF‐α. Angiotensin II may contribute, at least in part, to the early increased expression of TNF‐α mRNA in the obstructed kidney.

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