The anti-inflammatory activities of P53 in the vasculature have been associated with the enhancement of the endothelial barrier function. In the present study, we employed human and bovine lung endothelial cells, to investigate whether P53 expression levels affect the redox status of pulmonary cells. Moreover, we tested the possibility that those events affect the endothelial integrity of the lung microvascular monolayers. Our observations suggest that P53 suppression by LPS, pifithrin, or small interfering RNA increased the expression of the redox marker malondialdehyde. In contrast, P53 induction by Nutlin or the Hsp90 inhibitor AUY922 exerted the opposite effects, namely, suppressed that lipid oxidation marker. The direct measurement of the reactive oxygen species by 2,7-Dichlorodihydrofluorescein diacetate confirmed the antioxidant activity of P53 in the vasculature. Furthermore, the increased reactive oxygen species production due to P53 suppression was associated with lung hyperpermeability responses. In conclusion, P53 supports endothelial barrier function, at least in part, via the modulation of the reactive oxygen species.

中文翻译：

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P53调节肺内皮细胞的氧化还原状态。

P53在脉管系统中的抗炎活性与内皮屏障功能的增强有关。在本研究中，我们采用了人和牛的肺内皮细胞，以调查P53表达水平是否影响肺细胞的氧化还原状态。此外，我们测试了这些事件影响肺微血管单层内皮完整性的可能性。我们的观察结果表明，LPS，胃蛋白酶或小干扰RNA抑制P53会增加氧化还原标记物丙二醛的表达。相反，Nutlin或Hsp90抑制剂AUY922诱导P53发挥相反的作用，即抑制了脂质氧化标记。通过2直接测量活性氧 7-二氯二氢荧光素二乙酸酯证实了P53在脉管系统中的抗氧化活性。此外，由于P53抑制而增加的活性氧产生与肺通透性增高有关。总之，P53至少部分地通过调节活性氧来支持内皮屏障功能。