• Steven J Forrester, Qian Xu, Daniel S Kikuchi, Derick Okwan-Duodu, Ana Carolina Campos, Elizabeth A Faidley, Guogang Zhang, Bernard Lassègue, Ruxana T Sadikot, Kathy K Griendling, and Marina S Hernandes.
• Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA 30322, U.S.A.
• Clin. Sci. 2019 Jan 31; 133 (2): 321-334.

AbstractAcute respiratory distress syndrome (ARDS) in a deadly disease that can be brought on by endotoxins such as lipopolysaccharide (LPS). ARDS is characterized by vascular permeability, a severe inflammatory response, lung leukocyte infiltration, and resultant lung edema. Polymerase δ-interacting protein 2 (Poldip2) is a novel regulator of blood-brain barrier permeability; however, its role in regulating lung permeability and vascular inflammation is unknown. Here, the role of Poldip2 in regulating vascular permeability and inflammation in a mouse model of ARDS was assessed. Heterozygous deletion of Poldip2 was found to reduce LPS-induced mortality within 20 h, lung inflammatory signaling, and leukocyte infiltration. Moreover, reduced Poldip2-suppressed LP-induced vascular cell adhesion molecule (VCAM)-1 induction, leukocyte recruitment, and mitochondrial reactive oxygen species (ROS) production in vitro These data indicate that Poldip2 is an important regulator of the debilitating consequences of ARDS, potentially through the regulation of mitochondrial ROS-induced inflammatory signaling. Consequently, inhibition of Poldip2 may be a viable option for therapeutic discovery moving forward.© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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