p52 Overexpression Increases Epithelial Apoptosis, Enhances Lung Injury, and Reduces Survival after Lipopolysaccharide Treatment

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jamie A SaxonTimothy S Blackwell

Abstract

Although numerous studies have demonstrated a critical role for canonical NF-κB signaling in inflammation and disease, the function of the noncanonical NF-κB pathway remains ill-defined. In lung tissue from patients with acute respiratory distress syndrome, we identified increased expression of the noncanonical pathway component p100/p52. To investigate the effects of p52 expression in vivo, we generated a novel transgenic mouse model with inducible expression of p52 in Clara cell secretory protein-expressing airway epithelial cells. Although p52 overexpression alone did not cause significant inflammation, p52 overexpression caused increased lung inflammation, injury, and mortality following intratracheal delivery of Escherichia coli LPS. No differences in cytokine/chemokine expression were measured between p52-overexpressing mice and controls, but increased apoptosis of Clara cell secretory protein-positive airway epithelial cells was observed in transgenic mice after LPS stimulation. In vitro studies in lung epithelial cells showed that p52 overexpression reduced cell survival and increased the expression of several proapoptotic genes during cellular stress. Collectively, these studies demonstrate a novel role for p52 in cell...Continue Reading

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Citations

Mar 23, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shu-Hong DongZhi-Dong Han
Aug 25, 2017·International Journal of Molecular Sciences·Jin AnCheon Woong Choi
Jun 9, 2016·World Journal of Gastroenterology : WJG·Ying-Ying QiaoHong-Wei Xu
Apr 23, 2017·Molecular and Cellular Biochemistry·Peethambaran DivyaMohammed Azharuddin Savanur
Apr 19, 2018·Scientific Reports·Jamie A SaxonTimothy S Blackwell
Nov 10, 2020·Frontiers in Immunology·Chanan MeydanHermona Soreq
Sep 3, 2019·Chemical Research in Toxicology·Adam M SpeenIlona Jaspers

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis