P53 in acute respiratory distress syndrome
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Cellular and Molecular Life Sciences
COMMENTARY
P53 in acute respiratory distress syndrome Nektarios Barabutis1 Received: 4 June 2020 / Revised: 29 July 2020 / Accepted: 21 August 2020 © Springer Nature Switzerland AG 2020
Abstract P53 is a tumor suppressor protein, associated with strong anti-inflammatory activities. Recent evidence suggest that this transcription factor counteracts lung inflammatory diseases, including the lethal acute respiratory distress syndrome. Herein we provide a brief discussion on the relevant topic. Keywords Inflammation · Acute lung injury · Unfolded protein response · Heat shock proteins The severities of the acute respiratory distress syndrome (ARDS), including the ARDS related to COVID19, are associated with thousands of deaths worldwide. The current therapeutic approaches do not suffice to reduce the unacceptably high mortality rates of that lethal disorder. Hence, intense efforts are oriented towards the development of efficient medical countermeasures. Since lung endothelial hyper-permeability due to the “cytokine storm” is both a cause and consequence of ARDS, the elucidation of the mechanisms involved in the regulation of the lung endothelium is of the utmost need. Delineation of the molecular signaling governing the vascular barrier function may deliver new and exciting therapeutic possibilities for those patients in need [1]. P53 is an anti-inflammatory transcription factor, which devises cellular responses against a diverse variety of environmental stimuli. Indeed, it is subjected to a reciprocal regulation with the nuclear factor-kappa B (NF-κΒ). The exact nature of those interrelations has been recently described in a recent exceptional study by Carra et al. [2]. The proficient investigators explored the great depths of the tumoral P53/ NF-κB network and released their own perspectives in the corresponding field [2]. P53 counteracts stress by promoting cell death, senescence, or cell cycle arrest by utilizing oxidative phosphorylation. NF‐κB initiates immune responses by aerobic * Nektarios Barabutis [email protected] 1
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA
glycolysis [3]. The activation of one of those proteins results in the deactivation of the other, hence inhibition of NF-κΒ results in the activation of P53 functions [4]. Chronic infections by mycoplasma as well as NF-κΒ-activating peptides reduce P53, contributing to the progression of malignant transformations [5]. P53 is required for the repression of NF-κB by the glucocorticoid receptor [6], and P53 deficiency in mice was shown to potentiate the LPS-induced inflammation [7]. Moreover, P53 inhibits inflammation by antagonizing NF-κB [8]. The anti-inflammatory activities of P53 in human pathophysiology are not limited to cancer tissues. Indeed, it appears that this transcription factor exerts the capacity to protect against the LPS-induced lung endothelial hyperpermeability, by suppressing th
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