Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Corso Raffaello 33, 10125 Turin, Italy.
Inflamm Res. 2012 Apr;61(4):311-7. doi: 10.1007/s00011-011-0412-8. Epub 2012 Jan 6.
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.
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.
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.
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.
血管紧张素（Ang）II 和肿瘤坏死因子（TNF）-α 水平升高与肾小球损伤的发病机制有关，通过影响足细胞起作用。本研究旨在研究人足细胞中 Ang II-TNF-α 关系。
将永生化足细胞在无或有氯沙坦或 PD123,319（均为 100nM）、AT（1）和 AT（2）受体拮抗剂的情况下，分别暴露于 Ang II 中 6 天。
Ang II 在至少 72 小时的重复处理后，以双相模式增加基础 TNFA 基因表达和细胞因子释放，并在 10 nM 时达到最大反应。氯沙坦在整个实验期间抑制了 Ang II 对 TNF-α 产生的影响，表明 AT（1）受体的贡献。PD123,319 影响第二 TNF-α 产生高峰，也显示 AT（2）受体的贡献。此外，Ang II 以时间依赖性方式引起肿瘤坏死因子受体（TNFR）1 和 TNFR2 的过度表达。当 Ang II 的促增殖作用被中和 TNF-α 抗体拮抗时，证明了 Ang II 和 TNF-α 之间的功能相互作用。
我们的结果表明 Ang II 和 TNF-α 之间存在功能相互作用，并表明该细胞因子作为 Ang II 长期适应病理性足细胞变化的介质。
