The Mitochondria-Regulated Death Pathway Mediates Asbestos-Induced Alveolar Epithelial Cell Apoptosis

2003 ◽  
Vol 28 (2) ◽  
pp. 241-248 ◽  
Author(s):  
Vijayalakshmi Panduri ◽  
Sigmund A. Weitzman ◽  
Navdeep Chandel ◽  
David W. Kamp
Keyword(s):  
Epithelial Cell ◽  
Cell Apoptosis ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial ◽  
Epithelial Cell Apoptosis

scholarly journals GRP78 silencing enhances hyperoxia-induced alveolar epithelial cell apoptosis via CHOP pathway

2017 ◽  
Vol 16 (2) ◽  
pp. 1493-1501 ◽  
Author(s):  
Hong-Yan Lu ◽  
Xiao-Qing Chen ◽  
Wei Tang ◽  
Qiu-Xia Wang ◽  
Jie Zhang
Keyword(s):  
Epithelial Cell ◽  
Cell Apoptosis ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial ◽  
Epithelial Cell Apoptosis

scholarly journals Critical Roles of Inflammation and Apoptosis in Improved Survival in a Model of Hyperoxia-Induced Acute Lung Injury in Pneumocystis murina-Infected Mice

2009 ◽  
Vol 77 (3) ◽  
pp. 1053-1060 ◽  
Author(s):  
James M. Beck ◽  
Angela M. Preston ◽  
Steven E. Wilcoxen ◽  
Susan B. Morris ◽  
Anne Sturrock ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Lung Injury ◽  
Cell Apoptosis ◽  
Fas Ligand ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Gm Csf ◽  
Epithelial Cell Apoptosis ◽  
Ligand Expression

ABSTRACT Pneumocystis infections increase host susceptibility to additional insults that would be tolerated in the absence of infection, such as hyperoxia. In an in vivo model using CD4-depleted mice, we previously demonstrated that Pneumocystis murina pneumonia causes significant mortality following an otherwise nonlethal hyperoxic insult. Infected mice demonstrated increased pulmonary inflammation and alveolar epithelial cell apoptosis compared to controls. To test the mechanisms underlying these observations, we examined expression of components of the Fas-Fas ligand pathway in P. murina-infected mice exposed to hyperoxia. Hyperoxia alone increased expression of Fas on the surface of type II alveolar epithelial cells; conversely, infection with P. murina led to increased lung expression of Fas ligand. We hypothesized that inhibition of inflammatory responses or direct inhibition of alveolar epithelial cell apoptosis would improve survival in P. murina-infected mice exposed to hyperoxia. Mice were depleted of CD4+ T cells and infected with P. murina and then were exposed to >95% oxygen for 4 days, followed by return to normoxia. Experimental groups received vehicle, dexamethasone, or granulocyte-macrophage colony-stimulating factor (GM-CSF). Compared with the vehicle-treated group, treatment with dexamethasone reduced Fas ligand expression and significantly improved survival. Similarly, treatment with GM-CSF, an agent we have shown protects alveolar epithelial cells against apoptosis, decreased Fas ligand expression and also improved survival. Our results suggest that the dual stresses of P. murina infection and hyperoxia induce lung injury via activation of the Fas-Fas ligand pathway and that corticosteroids and GM-CSF reduce mortality in P. murina-infected mice exposed to hyperoxic stress by inhibition of inflammation and apoptosis.

Death-associated Protein Kinase 1 Mediates Ventilator-induced Lung Injury in Mice by Promoting Alveolar Epithelial Cell Apoptosis

2020 ◽  
Vol 133 (4) ◽  
pp. 905-918
Author(s):  
Yaxin Wang ◽  
Yiyi Yang ◽  
Lin Chen ◽  
Wei Xiong ◽  
Limin Song ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Lung Injury ◽  
Tidal Volume ◽  
Cell Apoptosis ◽  
Alveolar Epithelial Cell ◽  
B Cell Lymphoma ◽  
Cyclic Stretch ◽  
Alveolar Epithelial ◽  
Ventilator Induced Lung Injury ◽  
Epithelial Cell Apoptosis

Background Alveolar epithelial cell apoptosis is implicated in the onset of ventilator-induced lung injury. Death-associated protein kinase 1 (DAPK1) is associated with cell apoptosis. The hypothesis was that DAPK1 participates in ventilator-induced lung injury through promoting alveolar epithelial cell apoptosis. Methods Apoptosis of mouse alveolar epithelial cell was induced by cyclic stretch. DAPK1 expression was altered (knockdown or overexpressed) in vitro by using a small interfering RNA or a plasmid, respectively. C57/BL6 male mice (n = 6) received high tidal volume ventilation to establish a lung injury model. Adeno-associated virus transfection of short hairpin RNA and DAPK1 inhibitor repressed DAPK1 expression and activation in lungs, respectively. The primary outcomes were alveolar epithelial cell apoptosis and lung injury. Results Compared with the control group, the 24-h cyclic stretch group showed significantly higher alveolar epithelial cell apoptotic percentage (45 ± 4% fold vs. 6 ± 1% fold; P < 0.0001) and relative DAPK1 expression, and this group also demonstrated a reduced apoptotic percentage after DAPK1 knockdown (27 ± 5% fold vs. 53 ± 8% fold; P < 0.0001). A promoted apoptotic percentage in DAPK1 overexpression was observed without stretching (49 ± 6% fold vs. 14 ± 3% fold; P < 0.0001). Alterations in B-cell lymphoma 2 and B-cell lymphoma 2–associated X are associated with DAPK1 expression. The mice subjected to high tidal volume had higher DAPK1 expression and alveolar epithelial cell apoptotic percentage in lungs compared with the low tidal volume group (43 ± 6% fold vs. 4 ± 2% fold; P < 0.0001). Inhibition of DAPK1 through adeno-associated virus infection or DAPK1 inhibitor treatment appeared to be protective against lung injury with reduced lung injury score, resolved pulmonary inflammation, and repressed alveolar epithelial cell apoptotic percentage (47 ± 4% fold and 48 ± 6% fold; 35 ± 5% fold and 34 ± 4% fold; P < 0.0001, respectively). Conclusions DAPK1 promotes the onset of ventilator-induced lung injury by triggering alveolar epithelial cell apoptosis through intrinsic apoptosis pathway in mice. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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