scholarly journals The PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in chronic obstructive pulmonary disease caused by PM2.5 particulate matter

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052092791 ◽  
Author(s):  
Fang Zhang ◽  
Hui Ma ◽  
Zhong Lan Wang ◽  
Wei Hua Li ◽  
Hua Liu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Epithelial Cells ◽  
In Vitro Model ◽  
Mtor Pathway ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Alveolar Epithelial ◽  
Vitro Model

Objective Many lung diseases are associated with changes in autophagic activity. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a key regulatory role in autophagy. Our aim was to explore the function of PI3K/AKT/mTOR pathway on autophagy in chronic obstructive pulmonary disease (COPD) caused by particulate matter with a diameter <2.5 µm (PM2.5). Methods Male C57BL/6 mice were randomly divided into sham, model, and PI3K inhibitor groups. Mice were exposed to PM2.5 for 4 weeks to establish an in vivo COPD model. Alveolar epithelial cells were stimulated with PM2.5 to establish an in vitro COPD model. Results In mice with COPD induced by PM2.5, the PI3K inhibitor PF-04979064 suppressed protein expression of PI3K, p-AKT, and p-mTOR to increase apoptosis of alveolar epithelial cells and reduce autophagy. Short interfering PI3K suppressed the PI3K/AKT/mTOR pathway to induce apoptosis and reduce autophagy of alveolar epithelial cells in an in vitro model of COPD. Activation of PI3K induced the PI3K/AKT/mTOR pathway to reduce apoptosis of alveolar epithelial cells in the in vitro model of COPD by promoting autophagy. Conclusions These data demonstrate that PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in COPD.

Monolayers of porcine alveolar epithelial cells in primary culture as an in vitro model for drug absorption studies

2007 ◽  
Vol 66 (3) ◽  
pp. 372-382 ◽  
Author(s):  
Anne Steimer ◽  
Helmut Franke ◽  
Eleonore Haltner-Ukomado ◽  
Michael Laue ◽  
Carsten Ehrhardt ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Primary Culture ◽  
Drug Absorption ◽  
In Vitro Model ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Absorption Studies ◽  
Vitro Model

scholarly journals Adipose Tissue-Derived Stem Cells Have the Ability to Differentiate into Alveolar Epithelial Cells and Ameliorate Lung Injury Caused by Elastase-Induced Emphysema in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Eriko Fukui ◽  
Soichiro Funaki ◽  
Kenji Kimura ◽  
Toru Momozane ◽  
Atsuomi Kimura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Alveolar Cells ◽  
Alveolar Epithelial

Chronic obstructive pulmonary disease is a leading cause of mortality globally, with no effective therapy yet established. Adipose tissue-derived stem cells (ADSCs) are useful for ameliorating lung injury in animal models. However, whether ADSCs differentiate into functional cells remains uncertain, and no study has reported on the mechanism by which ADSCs improve lung functionality. Thus, in this study, we examined whether ADSCs differentiate into lung alveolar cells and are able to ameliorate lung injury caused by elastase-induced emphysema in model mice. Here, we induced ADSCs to differentiate into type 2 alveolar epithelial cells in vitro. We demonstrated that ADSCs can differentiate into type 2 alveolar epithelial cells in an elastase-induced emphysematous lung and that ADSCs improve pulmonary function of emphysema model mice, as determined with spirometry and 129Xe MRI. These data revealed a novel function for ADSCs in promoting repair of the damaged lung by direct differentiation into alveolar epithelial cells.

scholarly journals Human lung cDC1 drive increased perforin-mediated NK cytotoxicity in Chronic Obstructive Pulmonary Disease

2021 ◽  
Author(s):  
Alexander M Pallazola ◽  
Jessica X Rao ◽  
Dawit T Mengistu ◽  
Maria S Morcos ◽  
Mariam S Toma ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Pulmonary Disease ◽  
Human Lung ◽  
Airway Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

In chronic obstructive pulmonary disease (COPD), lung natural killer cells (NKs) lyse autologous lung epithelial cells in vitro, but underlying mechanisms and their relationship to epithelial cell apoptosis in vivo are undefined. Although this cytolytic capacity of lung NKs depends on priming by dendritic cells (DC), whether priming correlates with DC maturation or is limited to a specific DC subset are also unknown. We recruited ever-smokers (≥10 pack-years) (n=96) undergoing clinically-indicated lung resections. We analyzed lung NKs for cytotoxic molecule transcripts and for cytotoxicity, which we correlated with in situ detection of activated Caspase-3/7+ airway epithelial cells. To investigate DC priming, we measured lung DC expression of CCR2, CCR7, and CX3CR1, and co-cultured peripheral blood NKs with autologous lung DC, either matured using LPS (non-obstructed smokers) or separated into conventional DC type-1 (cDC1) versus cDC type-2 (cDC2) (COPD). Lung NKs in COPD expressed more perforin (p<0.02) and granzyme B (p<0.03) transcripts; inhibiting perforin blocked in vitro killing by lung NKs. Cytotoxicity in vitro correlated significantly (Sr=0.68, p=0.0043) with numbers of apoptotic epithelial cells per airway. In non-obstructed smokers, LPS-induced maturation enhanced DC-mediated priming of blood NKs, reflected by greater epithelial cell death. Although CCR7 expression was greater in COPD in both cDC1 (p<0.03) and cDC2 (p=0.009), only lung cDC1 primed NK killing. Thus, rather than being intrinsic to those with COPD, NK priming is a capacity of human lung DC that is inducible by recognition of bacterial (and possibly other) danger signals and restricted to the cDC1 subset.

scholarly journals Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 510
Author(s):  
Vitale Miceli ◽  
Alessandro Bertani ◽  
Cinzia Maria Chinnici ◽  
Matteo Bulati ◽  
Mariangela Pampalone ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
In Vitro Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Alveolar Epithelial Cells ◽  
Cold Ischemia ◽  
Human Amnion ◽  
Alveolar Epithelial ◽  
Vitro Model

The clinical results of lung transplantation (LTx) are still less favorable than other solid organ transplants in both the early and long term. The fragility of the lungs limits the procurement rate and can favor the occurrence of ischemia-reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) with Steen SolutionTM (SS) aims to address problems, and the implementation of EVLP to alleviate the activation of IRI-mediated processes has been achieved using mesenchymal stromal/stem cell (MSC)-based treatments. In this study, we investigated the paracrine effects of human amnion-derived MSCs (hAMSCs) in an in vitro model of lung IRI that includes cold ischemia and normothermic EVLP. We found that SS enriched by a hAMSC-conditioned medium (hAMSC-CM) preserved the viability and delayed the apoptosis of alveolar epithelial cells (A549) through the downregulation of inflammatory factors and the upregulation of antiapoptotic factors. These effects were more evident using the CM of 3D hAMSC cultures, which contained an increased amount of immunosuppressive and growth factors compared to both 2D cultures and encapsulated-hAMSCs. To conclude, we demonstrated an in vitro model of lung IRI and provided evidence that a hAMSC-CM attenuated IRI effects by improving the efficacy of EVLP, leading to strategies for a potential implementation of this technique.

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