OBJECTIVE: High levels of both angiotensin (Ang) II and tumor necrosis factor (TNF)-α have been implicated in the pathogenesis of glomerular injury by affecting podocytes. The aim of this study was to investigate the Ang II-TNF-α relationship in human podocytes. METHODS: Immortalized podocytes were exposed to Ang II for 6 days in the absence or presence of either losartan or PD123,319 (both at 100 nM), AT(1) and AT(2) receptor antagonists, respectively. RESULTS: Ang II, after at least 72 h of repeated treatment, increased basal TNFA gene expression and cytokine release with a biphasic pattern and maximum response at 10 nM. Losartan dampened the effects of Ang II on TNF-α production throughout the experimental period, demonstrating an AT(1) receptor contribution. PD123,319 affected the second TNF-α production peak, showing also an AT(2) receptor contribution. Moreover, Ang II causes tumor necrosis factor receptor (TNFR) 1 and TNFR2 over-expression in a time-dependent manner. The functional interaction between Ang II and TNF-α was demonstrated when the pro-proliferative effect of Ang II was antagonized by a neutralizing TNF-α antibody. CONCLUSIONS: Our results show a functional interaction between Ang II and TNF-α and implicate this cytokine as a mediator in Ang II long-term pathoadaptive podocytes changes.

Angiotensin II induces tumor necrosis factor-alpha expressionand release from cultured human podocytes

ROSA, ARIANNA CAROLINA;RATTAZZI, LORENZA;MIGLIO, Gianluca;COLLINO, Massimo;FANTOZZI, Roberto
2012

Abstract

OBJECTIVE: High levels of both angiotensin (Ang) II and tumor necrosis factor (TNF)-α have been implicated in the pathogenesis of glomerular injury by affecting podocytes. The aim of this study was to investigate the Ang II-TNF-α relationship in human podocytes. METHODS: Immortalized podocytes were exposed to Ang II for 6 days in the absence or presence of either losartan or PD123,319 (both at 100 nM), AT(1) and AT(2) receptor antagonists, respectively. RESULTS: Ang II, after at least 72 h of repeated treatment, increased basal TNFA gene expression and cytokine release with a biphasic pattern and maximum response at 10 nM. Losartan dampened the effects of Ang II on TNF-α production throughout the experimental period, demonstrating an AT(1) receptor contribution. PD123,319 affected the second TNF-α production peak, showing also an AT(2) receptor contribution. Moreover, Ang II causes tumor necrosis factor receptor (TNFR) 1 and TNFR2 over-expression in a time-dependent manner. The functional interaction between Ang II and TNF-α was demonstrated when the pro-proliferative effect of Ang II was antagonized by a neutralizing TNF-α antibody. CONCLUSIONS: Our results show a functional interaction between Ang II and TNF-α and implicate this cytokine as a mediator in Ang II long-term pathoadaptive podocytes changes.
61
311
317
angiotensin II, podocytes, inflammation
Rosa AC; Rattazzi L; Miglio G; Collino M; Fantozzi R
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/100646
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