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 TRIM72 is required for effective repair of alveolar epithelial cell wounding

2014 ◽  
Vol 307 (6) ◽  
pp. L449-L459 ◽  
Author(s):  
Seong Chul Kim ◽  
Thomas Kellett ◽  
Shaohua Wang ◽  
Miyuki Nishi ◽  
Nagaraja Nagre ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Striated Muscle ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Lung Cells ◽  
Alveolar Epithelial ◽  
High Tidal Volume Ventilation

The molecular mechanisms for lung cell repair are largely unknown. Previous studies identified tripartite motif protein 72 (TRIM72) from striated muscle and linked its function to tissue repair. In this study, we characterized TRIM72 expression in lung tissues and investigated the role of TRIM72 in repair of alveolar epithelial cells. In vivo injury of lung cells was introduced by high tidal volume ventilation, and repair-defective cells were labeled with postinjury administration of propidium iodide. Primary alveolar epithelial cells were isolated and membrane wounding and repair were labeled separately. Our results show that absence of TRIM72 increases susceptibility to deformation-induced lung injury whereas TRIM72 overexpression is protective. In vitro cell wounding assay revealed that TRIM72 protects alveolar epithelial cells through promoting repair rather than increasing resistance to injury. The repair function of TRIM72 in lung cells is further linked to caveolin 1. These data suggest an essential role for TRIM72 in repair of alveolar epithelial cells under plasma membrane stress failure.

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.

Injury of rat pulmonary alveolar epithelial cells by H2O2: dependence on phenotype and catalase

1991 ◽  
Vol 260 (4) ◽  
pp. L318-L325 ◽  
Author(s):  
R. H. Simon ◽  
J. A. Edwards ◽  
M. M. Reza ◽  
R. G. Kunkel
Keyword(s):  
Epithelial Cells ◽  
Catalase Activity ◽  
Lung Diseases ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial

In a variety of inflammatory lung diseases, type I alveolar epithelial cells are more likely to be injured than are type II cells. Because oxidants have been implicated as a cause of injury in various inflammatory lung diseases, we evaluated the effects of differentiation on alveolar epithelial cell susceptibility to H2O2-induced injury. With the use of isolated rat type II cells in culture, we found that the cytotoxic effect of H2O2 increased between days 2 and 7, when type II cells are known to lose their distinctive type II properties and assume a more type I-like appearance. We previously reported that type II cells utilized both intracellular catalase and glutathione-dependent reactions to protect against H2O2. We therefore examined whether alterations in either of these protective mechanisms were responsible for the differentiation-dependent changes in sensitivity to H2O2. We found that catalase activity within alveolar epithelial cells decreased between 2 and 7 days in culture, whereas no changes were detected in glutathione-dependent systems. We then used a histochemical technique that detects catalase activity and found that type II cells within rat lungs possessed numerous catalase-containing peroxisomes, whereas very few were detected in type I cells. These findings demonstrate that as type II cells assume a type I-like phenotype, they become more susceptible to H2O2-induced injury. This increased susceptibility is associated with reductions in intracellular catalase activity, both in vitro and in vivo.

scholarly journals LPS-induced depolymerization of cytoskeleton and its role in TNF-α production by rat pneumocytes

1999 ◽  
Vol 277 (3) ◽  
pp. L606-L615 ◽  
Author(s):  
Noritaka Isowa ◽  
Alexandre M. Xavier ◽  
Ewa Dziak ◽  
Michal Opas ◽  
Donna I. McRitchie ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Cells ◽  
Protein Production ◽  
Mrna Level ◽  
Alveolar Epithelial Cells ◽  
Immunofluorescent Staining ◽  
Alveolar Epithelial ◽  
Tnf Α ◽  
Factor Α

Lipopolysaccharide (LPS) polymerizes microfilaments and microtubules in macrophages and monocytes. Disrupting microfilaments or microtubules with cytochalasin D (CytoD) or colchicine can suppress LPS-induced tumor necrosis factor-α (TNF-α) gene expression and protein production from these cells. We have recently demonstrated that primary cultured rat alveolar epithelial cells can produce TNF-α on LPS stimulation. In the present study, we found that the LPS-induced increase in TNF-α mRNA level and protein production in alveolar epithelial cells was not inhibited by CytoD or colchicine (1 nM to 10 μM). In fact, LPS-induced TNF-α production was further enhanced by CytoD (1–10 μM) and inhibited by jasplakinolide, a polymerizing agent for microfilaments. Immunofluorescent staining and confocal microscopy showed that LPS (10 μg/ml) depolymerized microfilaments and microtubules within 15 min, which was prolonged until 24 h for microfilaments. These results suggest that the effects of LPS on the cytoskeleton and the role of the cytoskeleton in mediating TNF-α production in alveolar epithelial cells are opposite to those in immune cells. This disparity may reflect the different roles between nonimmune and immune cells in host defense.

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.

Design of biomimetic substrates for long-term maintenance of alveolar epithelial cells

2018 ◽  
Vol 6 (2) ◽  
pp. 292-303 ◽  
Author(s):  
James C. H. Poon ◽  
Zhongfa Liao ◽  
Takaya Suzuki ◽  
Miranda M. Carleton ◽  
John P. Soleas ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Diseases ◽  
Alveolar Epithelial Cells ◽  
Biological Mechanisms ◽  
Alveolar Epithelial ◽  
Epithelial Culture ◽  
Culture Models ◽  
Term Maintenance

There is a need to establish in vitro lung alveolar epithelial culture models to better understand the fundamental biological mechanisms that drive lung diseases.

Altered expression of tight junction molecules in alveolar septa in lung injury and fibrosis

2012 ◽  
Vol 302 (2) ◽  
pp. L193-L205 ◽  
Author(s):  
Hiromitsu Ohta ◽  
Shigeki Chiba ◽  
Masahito Ebina ◽  
Mikio Furuse ◽  
Toshihiro Nukiwa
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Tight Junction ◽  
Tight Junctions ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Alveolar Epithelial Cells ◽  
Altered Expression ◽  
Alveolar Epithelial

The dysfunction of alveolar barriers is a critical factor in the development of lung injury and subsequent fibrosis, but the underlying molecular mechanisms remain poorly understood. To clarify the pathogenic roles of tight junctions in lung injury and fibrosis, we examined the altered expression of claudins, the major components of tight junctions, in the lungs of disease models with pulmonary fibrosis. Among the 24 known claudins, claudin-1, claudin-3, claudin-4, claudin-7, and claudin-10 were identified as components of airway tight junctions. Claudin-5 and claudin-18 were identified as components of alveolar tight junctions and were expressed in endothelial and alveolar epithelial cells, respectively. In experimental bleomycin-induced lung injury, the levels of mRNA encoding tight junction proteins were reduced, particularly those of claudin-18. The integrity of the epithelial tight junctions was disturbed in the fibrotic lesions 14 days after the intraperitoneal instillation of bleomycin. These results suggest that bleomycin mainly injured alveolar epithelial cells and impaired alveolar barrier function. In addition, we analyzed the influence of transforming growth factor-β (TGF-β), a critical mediator of pulmonary fibrosis that is upregulated after bleomycin-induced lung injury, on tight junctions in vitro. The addition of TGF-β decreased the expression of claudin-5 in human umbilical vein endothelial cells and disrupted the tight junctions of epithelial cells (A549). These results suggest that bleomycin-induced lung injury causes pathogenic alterations in tight junctions and that such alterations seem to be induced by TGF-β.

scholarly journals p53-Fibrinolytic system and acute lung injury

Biologia ◽  
2016 ◽  
Vol 71 (10) ◽  
Author(s):  
Yashodhar Prabhakar Bhandary
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Plasminogen Activator ◽  
Lung Diseases ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Fibrinolytic System ◽  
Alveolar Epithelial ◽  
Pai 1

AbstractA different form of lung disease including acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome, bronchiolitis, interstitial lung diseases and drug-induced lung diseases are often associated with alveolar epithelial cell apoptosis. Epithelial cells that are the prime important cell in the alveolar architecture produce fibrinolytic components, such as urokinase-type plasminogen activator (uPA), its receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and tumor suppressor protein p53. The increased expression of p53, which is responsible for apoptosis of alveolar epithelial cells, and the other components of the fibrinolytic system, and a decreased alveolar fibrinolysis, are strongly involved in the pathogenesis of ALI. The fibrinolytic system, such as uPA, uPAR and PAI-1 interaction with p53, brings about the regulation of the signaling response, as well as the fibrinolytic properties, which will be useful in maintaining the unity of the cell, and also providing the signals to the cells on whether they undergo apoptosis or survival after ALI.

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.

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