scholarly journals NLRP3 deletion protects from hyperoxia-induced acute lung injury

2013 ◽  
Vol 305 (2) ◽  
pp. C182-C189 ◽  
Author(s):  
Jutaro Fukumoto ◽  
Itsuko Fukumoto ◽  
Prasanna Tamarapu Parthasarathy ◽  
Ruan Cox ◽  
Bao Huynh ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Epithelial Cell ◽  
Inflammasome Activation ◽  
Nlrp3 Gene ◽  
Lung Epithelial ◽  
Epithelial Cell Death

Inspiration of a high concentration of oxygen, a therapy for acute lung injury (ALI), could unexpectedly lead to reactive oxygen species (ROS) production and hyperoxia-induced acute lung injury (HALI). Nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) senses the ROS, triggering inflammasome activation and interleukin-1β (IL-1β) production and secretion. However, the role of NLRP3 inflammasome in HALI is unclear. The main aim of this study is to determine the effect of NLRP3 gene deletion on inflammatory response and lung epithelial cell death. Wild-type (WT) and NLRP3−/− mice were exposed to 100% O2 for 48–72 h. Bronchoalveolar lavage fluid and lung tissues were examined for proinflammatory cytokine production and lung inflammation. Hyperoxia-induced lung pathological score was suppressed in NLRP3−/− mice compared with WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1β, TNFα, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 were attenuated in NLRP3−/− mice. NLRP3 deletion decreased lung epithelial cell death and caspase-3 levels and a suppressed NF-κB levels compared with WT controls. Taken together, this research demonstrates for the first time that NLRP3-deficient mice have suppressed inflammatory response and blunted lung epithelial cell apoptosis to HALI.

scholarly journals Platelets inhibit apoptotic lung epithelial cell death and protect mice against infection-induced lung injury

2019 ◽  
Vol 3 (3) ◽  
pp. 432-445 ◽  
Author(s):  
William Bain ◽  
Tolani Olonisakin ◽  
Minting Yu ◽  
Yanyan Qu ◽  
Mei Hulver ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Lung Epithelial Cell ◽  
Barrier Disruption ◽  
Lung Epithelial ◽  
Epithelial Cell Death ◽  
Alveolar Capillary

Abstract Thrombocytopenia is associated with worse outcomes in patients with acute respiratory distress syndrome, which is most commonly caused by infection and marked by alveolar–capillary barrier disruption. However, the mechanisms by which platelets protect the lung alveolar–capillary barrier during infectious injury remain unclear. We found that natively thrombocytopenic Mpl−/− mice deficient in the thrombopoietin receptor sustain severe lung injury marked by alveolar barrier disruption and hemorrhagic pneumonia with early mortality following acute intrapulmonary Pseudomonas aeruginosa (PA) infection; barrier disruption was attenuated by platelet reconstitution. Although PA infection was associated with a brisk neutrophil influx, depletion of airspace neutrophils failed to substantially mitigate PA-triggered alveolar barrier disruption in Mpl−/− mice. Rather, PA cell-free supernatant was sufficient to induce lung epithelial cell apoptosis in vitro and in vivo and alveolar barrier disruption in both platelet-depleted mice and Mpl−/− mice in vivo. Cell-free supernatant from PA with genetic deletion of the type 2 secretion system, but not the type 3 secretion system, mitigated lung epithelial cell death in vitro and lung injury in Mpl−/− mice. Moreover, platelet releasates reduced poly (ADP ribose) polymerase cleavage and lung injury in Mpl−/− mice, and boiling of platelet releasates, but not apyrase treatment, abrogated PA supernatant–induced lung epithelial cell cytotoxicity in vitro. These findings indicate that while neutrophil airspace influx does not potentiate infectious lung injury in the thrombocytopenic host, platelets and their factors protect against severe pulmonary complications from pathogen-secreted virulence factors that promote host cell death even in the absence of overt infection.

scholarly journals Sirtuin 1 Promotes Hyperoxia-Induced Lung Epithelial Cell Death Independent of NF-E2–Related Factor 2 Activation

2016 ◽  
Vol 54 (5) ◽  
pp. 697-706 ◽  
Author(s):  
Haranatha R. Potteti ◽  
Subbiah Rajasekaran ◽  
Senthilkumar B. Rajamohan ◽  
Chandramohan R. Tamatam ◽  
Narsa M. Reddy ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Epithelial Cell ◽  
Sirtuin 1 ◽  
Related Factor ◽  
Lung Epithelial ◽  
Epithelial Cell Death

Regulated in Development and DNA Damage Response 1 Knockdown Alleviates Lipopolysaccharide-Induced Acute Lung Injury

2021 ◽  
Vol 11 (7) ◽  
pp. 1333-1338
Author(s):  
Han Han ◽  
Zhenxi Yu ◽  
Mei Feng
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Cell Activity ◽  
Lung Epithelial Cells ◽  
Lung Epithelial Cell ◽  
Inflammatory Factors ◽  
Lung Epithelial ◽  
Damage Response

Regulated in Development and DNA Damage Response 1 (REDD1) knockdown can reduce the endoplasmic reticulum stress response in liver injury. However, its role on lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored. This study aimed to evaluate the effect of REDD1 on lung epithelial cells induced by LPS. Rt-qPCR and Western blot were used to detect REDD1 expression in 16HBE cells induced by LPS. The interfering REDD1 plasmid was constructed, and CCK8 was used to detect the effect of interference with REDD1 on LPS-induced lung epithelial cell activity. The expression of inflammatory factors was detected by ELISA and the apoptotic level was detected by TUNEL staining. String database was used to predict the combination of REDD1 and EP300 in lung epithelial cells, which was verified by CoIP experiment. An overexpressed plasmid of EP300 was constructed to detect the effects of EP300 on inflammatory factors and apoptosis in REDD1 lung epithelial cells. LPS-induced increased REDD1 expression in lung epithelial cells. Interference with REDD1 inhibits LPS-induced lung epithelial cell activity injury and inflammatory factor expression and inhibits LPS-induced lung epithelial cell apoptosis. After interference with REDD1, the expression of EP300 in LPS-induced lung epithelial cells was inhibited, and the overexpression of EP300 was reversed to promote the production of inflammatory factors and apoptosis. In conclusion, these results demonstrate that REDD1 knockdown alleviates LPS-induced acute lung injury.

scholarly journals Endotoxin stabilizes protein arginine methyltransferase 4 (PRMT4) protein triggering death of lung epithelia

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Yandong Lai ◽  
Xiuying Li ◽  
Tiao Li ◽  
Toru Nyunoya ◽  
Kong Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Tissue Injury ◽  
Respiratory Illness ◽  
Limited Data ◽  
Arginine Methyltransferase ◽  
Lung Epithelial ◽  
Injury Models ◽  
Epithelial Cell Death

AbstractLung epithelial cell death is a prominent feature of acute lung injury and acute respiratory distress syndrome (ALI/ARDS), which results from severe pulmonary infection leading to respiratory failure. Multiple mechanisms are believed to contribute to the death of epithelia; however, limited data propose a role for epigenetic modifiers. In this study, we report that a chromatin modulator protein arginine N-methyltransferase 4/coactivator-associated arginine methyltransferase 1 (PRMT4/CARM1) is elevated in human lung tissues with pneumonia and in experimental lung injury models. Here PRMT4 is normally targeted for its degradation by an E3 ubiquitin ligase, SCFFBXO9, that interacts with PRMT4 via a phosphodegron to ubiquitinate the chromatin modulator at K228 leading to its proteasomal degradation. Bacterial-derived endotoxin reduced levels of SCFFBXO9 thus increasing PRMT4 cellular concentrations linked to epithelial cell death. Elevated PRMT4 protein caused substantial epithelial cell death via caspase 3-mediated cell death signaling, and depletion of PRMT4 abolished LPS-mediated epithelial cell death both in cellular and murine injury models. These findings implicate a unique molecular interaction between SCFFBXO9 and PRMT4 and its regulation by endotoxin that impacts the life span of lung epithelia, which may play a key role in the pathobiology of tissue injury observed during critical respiratory illness.

Lung epithelial cell apoptosis during acute lung injury in infancy

2007 ◽  
Vol 8 (2) ◽  
pp. 132-137 ◽  
Author(s):  
Reinout A. Bem ◽  
Albert P. Bos ◽  
Gustavo Matute-Bello ◽  
Minke van Tuyl ◽  
Job B. M. van Woensel
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Cell Apoptosis ◽  
Lung Epithelial Cell ◽  
Lung Epithelial ◽  
Epithelial Cell Apoptosis
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