Luminespib counteracts the Kifunensine-induced lung endothelial barrier dysfunction

Abstract

Unfolded protein response (UPR) suppression by Kifunensine has been associated with lung hyperpermeability, the hallmark of Acute Respiratory Distress Syndrome. The present study investigates the effects of the heat shock protein 90 inhibitor Luminespib (AUY-922) towards the Kifunensine-triggered lung endothelial dysfunction. Our results indicate that the UPR inducer Luminespib counteracts the effects of Kifunensine in both human and bovine lung endothelial cells. Hence, we suggest that mild UPR induction may serve as a promising therapeutic strategy against potentially lethal respiratory disorders, including the ARDS related to COVID-19.

Keywords

• P53
• Endothelium
• Inflammation
• Acute lung injury