scholarly journals Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium Fusobacterium nucleatum in Human Respiratory Epithelial Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1352
Author(s):  
Yuwa Takahashi ◽  
Norihisa Watanabe ◽  
Noriaki Kamio ◽  
Sho Yokoe ◽  
Ryuta Suzuki ◽  
...  
Keyword(s):  
Risk Factor ◽  
Epithelial Cells ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Fusobacterium Nucleatum ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Global Public Health ◽  
Periodontopathic Bacteria ◽  
Alveolar Epithelial

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a risk factor for pneumonia and the exacerbation of chronic obstructive pulmonary disease, presumably because of the aspiration of saliva contaminated with periodontopathic bacteria into the lower respiratory tract. Patients with these diseases have increased rates of COVID-19 aggravation and mortality. Because periodontopathic bacteria have been isolated from the bronchoalveolar lavage fluid of patients with COVID-19, periodontitis may be a risk factor for COVID-19 aggravation. However, the molecular links between periodontitis and COVID-19 have not been clarified. In this study, we found that the culture supernatant of the periodontopathic bacterium Fusobacterium nucleatum (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells. CSF also strongly induced IL-6 and IL-8 expression by BEAS-2B bronchial epithelial cells and Detroit 562 pharyngeal epithelial cells. These results suggest that when patients with mild COVID-19 frequently aspirate periodontopathic bacteria, SARS-CoV-2 infection is promoted, and inflammation in the lower respiratory tract may become severe in the presence of viral pneumonia.

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.

Gene regulation in the adaptive process to hypoxia in lung epithelial cells

2009 ◽  
Vol 296 (3) ◽  
pp. L267-L274 ◽  
Author(s):  
Christine Clerici ◽  
Carole Planès
Keyword(s):  
Gene Regulation ◽  
Epithelial Cells ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Hypoxic Exposure ◽  
Chronic Obstructive ◽  
Low Oxygen ◽  
Alveolar Epithelial ◽  
Expression Of Genes

Lung alveolar epithelial cells are normally very well oxygenated but may be exposed to hypoxia in many pathological conditions such as pulmonary edema, acute respiratory distress syndrome, chronic obstructive pulmonary diseases, or in some environmental conditions such ascent to high altitude. The ability of alveolar epithelial cells to cope with low oxygen tensions is crucial to maintain the structural and functional integrity of the alveolar epithelium. Alveolar epithelial cells appear to be remarkably tolerant to oxygen deprivation as they are able to maintain adequate cellular ATP content during prolonged hypoxic exposure when mitochondrial oxidative phosphorylation is limited. This property mostly relies on the ability of the cells to rapidly modify their gene expression program, stimulating the expression of genes involved in anaerobic energy supply and repressing expression of genes involved in some ATP-consuming cellular processes. This adaptive strategy of the cells is mostly, but not entirely, dependent on the expression of hypoxia-inducible factors (HIFs), known to be responsible for orchestrating a large number of hypoxia-sensitive genes. This review focuses on the role of HIF isoforms expressed in alveolar epithelial cells exposed to hypoxia and on the specific hypoxic gene regulation that takes place in alveolar epithelial cells either through HIF-dependent or -independent pathways.

Adenoviral E1A primes alveolar epithelial cells to PM10-induced transcription of interleukin-8

2001 ◽  
Vol 281 (3) ◽  
pp. L598-L606 ◽  
Author(s):  
Peter S. Gilmour ◽  
Irfan Rahman ◽  
Shizu Hayashi ◽  
James C. Hogg ◽  
Kenneth Donaldson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Mrna Expression ◽  
Protein Release ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Alveolar Epithelial ◽  
Nuclear Binding ◽  
Increased Risk ◽  
Proinflammatory Responses

The presence of the adenoviral early region 1A (E1A) protein in human lungs has been associated with an increased risk of chronic obstructive pulmonary disease (COPD), possibly by a mechanism involving amplification of proinflammatory responses. We hypothesize that enhanced inflammation results from increased transcription factor activation in E1A-carrying cells, which may afford susceptibility to environmental particulate matter < 10 μm (PM10)-mediated oxidative stress. We measured interleukin (IL)-8 mRNA expression and protein release in human alveolar epithelial cells (A549) transfected with the E1A gene (E1A+ve). Both E1A+ve and −ve cells released IL-8 after incubation with TNF-α, but only E1A+ve cells were sensitive to LPS stimulation in IL-8 mRNA expression and protein release. E1A+ve cells showed an enhanced IL-8 mRNA and protein response after treatment with H2O2and PM10. E1A-enhanced induction of IL-8 was accompanied by increases in activator protein-1 and nuclear factor-κB nuclear binding in E1A+ve cells, which also showed higher basal nuclear binding of these transcription factors. These data suggest that the presence of E1A primes the cell transcriptional machinery for oxidative stress signaling and therefore facilitates amplification of proinflammatory responses. By this mechanism, susceptibility to exacerbation of COPD in response to particulate air pollution may occur in individuals harboring E1A.

scholarly journals Mesenchymal Stem Cell-Based Therapy of Inflammatory Lung Diseases: Current Understanding and Future Perspectives

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
C. Randall Harrell ◽  
Ruxana Sadikot ◽  
Jose Pascual ◽  
Crissy Fellabaum ◽  
Marina Gazdic Jankovic ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Cells ◽  
Lung Diseases ◽  
Molecular Mechanisms ◽  
Alveolar Epithelial Cells ◽  
Pulmonary Diseases ◽  
Chronic Obstructive ◽  
Future Perspectives ◽  
Alveolar Epithelial ◽  
Cell Based Therapy

During acute or chronic lung injury, inappropriate immune response and/or aberrant repair process causes irreversible damage in lung tissue and most usually results in the development of fibrosis followed by decline in lung function. Inhaled corticosteroids and other anti-inflammatory drugs are very effective in patients with inflammatory lung disorders, but their long-term use is associated with severe side effects. Accordingly, new therapeutic agents that will attenuate ongoing inflammation and, at the same time, promote regeneration of injured alveolar epithelial cells are urgently needed. Mesenchymal stem cells (MSCs) are able to modulate proliferation, activation, and effector function of all immune cells that play an important role in the pathogenesis of acute and chronic inflammatory lung diseases. In addition to the suppression of lung-infiltrated immune cells, MSCs have potential to differentiate into alveolar epithelial cells in vitro and, accordingly, represent new players in cell-based therapy of inflammatory lung disorders. In this review article, we described molecular mechanisms involved in MSC-based therapy of acute and chronic pulmonary diseases and emphasized current knowledge and future perspectives related to the therapeutic application of MSCs in patients suffering from acute respiratory distress syndrome, pneumonia, asthma, chronic obstructive pulmonary diseases, and idiopathic pulmonary fibrosis.

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.

Alveolar epithelial cells type II show a high sensitivity to cigarette smoke extract

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
S Seehase ◽  
B Baron-Luehr ◽  
C Kugler ◽  
E Vollmer ◽  
T Goldmann
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
High Sensitivity ◽  
Cigarette Smoke Extract ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
Alveolar Epithelial
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