Dysregulation of claudin-5 in HIV-induced interstitial pneumonitis and lung vascular injury. Protective role of peroxisome proliferator-activated receptor-γ.

American Journal of Respiratory and Critical Care Medicine
Hong LiGeorgette D Kanmogne

Abstract

HIV-1-induced interstitial pneumonitis (IP) is a serious complication of HIV-1 infection, characterized by inflammation and cellular infiltration in lungs, often leading to respiratory failure and death. The barrier function of the pulmonary endothelium is caused in part by tight junction (TJ) proteins, such as claudin-5. Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in lung tissues and regulates inflammation. We hypothesize that HIV-1 induces vascular lung injury, and HIV-1-mediated damage of the pulmonary endothelium and IP is associated with dysregulation of PPAR-γ. Investigate the effects of HIV-1 infection on the pulmonary microvasculature and the modulatory effects of the PPAR-γ ligands. Using human lung tissues, we demonstrated down-regulation of claudin-5 (marker of pulmonary barrier integrity), down-regulation of PPAR-γ transcription, and expression in lung tissues of HIV-1-infected humans with IP. Human lung microvascular endothelial cells expressed the TJ proteins claudin-5, ZO-1, and ZO-2; HIV-1 decreased TJ proteins expression and induced nuclear factor-κB promoter activity, which was reversed by PPAR-γ agonist. Using two murine HIV/AIDS models, we demonstrated decreased claudin-5 expression and ...Continue Reading

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Sep 16, 2015·American Journal of Respiratory and Critical Care Medicine·David S HuiPaul K S Chan
Oct 4, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanhui CaiMarcelo J Kuroda
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Mar 2, 2017·Histochemistry and Cell Biology·Andrea PeterStefan Hippenstiel
Apr 18, 2017·Annals of the New York Academy of Sciences·Lorenza González-MariscalFrancisco Cuellar-Perez
Aug 18, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Merilin Al Sharif

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