LPS-induced Acute Lung Injury Involves NF-κB–mediated Downregulation of SOX18

• DOI: 10.1165/rcmb.2016-0390oc
• Publication Date: 2017-11-08T14:56:26Z
• Authors: Christine M. Gross; Manuela Kellner; Ting Wang; Qing Lu; Xutong Sun; Evgeny A. Zemskov; Satish Noonepalle; Archana Kangath; Sanjiv Kumar; Manuel Gonzalez-G...; Ankit A. Desai; Saurabh Aggarwal; Boris Gorshkov; Christina Klinger; Alexander D. Verin; John D. Catravas; Jeffrey R. Jacobson; Jason X.-J. Yuan; Ruslan Rafikov; Joe G. N. Garcia; Stephen M. Black
• Keywords: Claudin

One of the early events in progression LPS-mediated acute lung injury mice is disruption pulmonary endothelial barrier resulting edema. However, molecular mechanisms by which becomes compromised remain unresolved. The SRY (sex-determining region on Y chromosome)-related high-mobility group box (Sox) F family member, SOX18, a barrier-protective protein through its ability to increase expression tight junction CLDN5. Thus, purpose this study was determine if downregulation SOX18-CLDN5 axis plays role associated with LPS exposure. Our data indicate that both SOX18 and CLDN5 decreased two models vivo exposure (intraperitoneal, intratracheal). A similar observed cultured human microvascular cells (HLMVECs) exposed LPS. overexpression HLMVECs or mouse attenuated vascular disruption. Conversely, reduced (siRNA) HLMVEC effects overexpression. mechanism decreases identified as transcriptional repression binding NF-κB (p65) promoter sequence located between -1,082 -1,073 bp peroxynitrite contributing activation. We conclude NF-κB-dependent are essentially involved cell integrity injury.