Angiotensin II receptor blocker inhibits tumour necrosis factor-alpha-induced cell damage in human renal proximal tubular epithelial cells

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Abstract

Aim

We investigated the effect of angiotensin II (AII) type 1 (AT1) and angiotensin II type 2 (AT2) receptor blockers on tumour necrosis factor alpha (TNF-α)-induced cell damage in human renal proximal tubular epithelial cells (RPTEC).

Methods

The lactate dehydrogenase (LDH) and N-acetyl-beta-glucosaminidase (NAG) release into the medium after TNF-α treatment in RPTEC were determined using modified commercial procedures. In addition, the levels of caspase 3/7 activity in RPTEC were measured after TNF-α treatment with ατ1 or AT2 receptor blockers. Finally we investigated the change of p22phox protein levels after TNF-α with ατ1 or AT2 receptor blockers in RPTEC.

Results

Tumour necrosis factor alpha (10−8 mol/L) significantly increased LDH and NAG release into the medium from RPTEC. ατ1 receptor blockers, olmesartan and valsartan (10−9−10−6 mol/L) showed a significant reduction on TNF-α-induced LDH and NAG release in RPTEC. AT2 receptor blocker, PD123319 (10−7−10−5 mol/L) also decreased TNF-α-induced LDH and NAG release in RPTEC. Blockade of both ατ1 and AT2 receptor indicated additional reduction on TNF-α-induced LDH and NAG release. TNF-α (10−8 mol/L) treatment showed small but significant increases of caspase 3/7 activity in RPTEC, and AT1 and AT2 receptor blockers (10−8 mol/L) comparably decreased TNF-α-induced caspase 3/7 activity. Significant increases of p22phox protein levels were observed in TNF-α-treated group in RPTEC. However, only ατ1 (10−8 mol/L) but not AT2 (10−5 mol/L) receptor blocker significantly decreased TNF-α-induced p22phox protein levels.

Conclusion

The present study demonstrates that TNF-α induces renal tubular cell damage in RPTEC and AT1/AT2 receptor blockers showed cytoprotective effects probably via at least partly different mechanism.

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