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.
Keywords: Acute lung injury; Barrier function; Endothelium; Inflammation.