scholarly journals Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-β-induced senescence of human bronchial epithelial cells

2011 ◽  
Vol 300 (3) ◽  
pp. L391-L401 ◽  
Author(s):  
Shunsuke Minagawa ◽  
Jun Araya ◽  
Takanori Numata ◽  
Satoko Nojiri ◽  
Hiromichi Hara ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cellular Senescence ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Pathological Finding ◽  
Bronchial Epithelial Cells ◽  
Type I ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Expression Levels

Reepithelialization of remodeled air spaces with bronchial epithelial cells is a prominent pathological finding in idiopathic pulmonary fibrosis (IPF) and is implicated in IPF pathogenesis. Recent studies suggest that epithelial senescence is a risk factor for development of IPF, indicating such reepithelialization may be influenced by the acceleration of cellular senescence. Among the sirtuin (SIRT) family, SIRT6, a class III histone deacetylase, has been demonstrated to antagonize senescence. We evaluated the senescence of bronchiolization in association with SIRT6 expression in IPF lung. Senescence-associated β-galactosidase staining and immunohistochemical detection of p21 were performed to evaluate cellular senescence. As a model for transforming growth factor (TGF)-β-induced senescence of abnormal reepithelialization, we used primary human bronchial epithelial cells (HBEC). The changes of SIRT6, p21, and interleukin (IL)-1β expression levels in HBEC, as well as type I collagen expression levels in fibroblasts, were evaluated. In IPF lung samples, an increase in markers of senescence and SIRT6 expression was found in the bronchial epithelial cells lining cystically remodeled air spaces. We found that TGF-β induced senescence in primary HBEC by increasing p21 expression, and, whereas TGF-β also induced SIRT6, it was not sufficient to inhibit cellular senescence. However, overexpression of SIRT6 efficiently inhibited TGF-β-induced senescence via proteasomal degradation of p21. TGF-β-induced senescent HBEC secreted increased amounts of IL-1β, which was sufficient to induce myofibroblast differentiation in fibroblasts. These findings suggest that accelerated epithelial senescence plays a role in IPF pathogenesis through perpetuating abnormal epithelial-mesenchymal interactions, which can be antagonized by SIRT6.

Human bronchial epithelial cells can contract type I collagen gels

1998 ◽  
Vol 274 (1) ◽  
pp. L58-L65 ◽  
Author(s):  
Xiangde Liu ◽  
Takeshi Umino ◽  
Marty Cano ◽  
Ronald Ertl ◽  
Tom Veys ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Type I Collagen ◽  
Bronchial Epithelial Cells ◽  
Image Analyzer ◽  
Type I ◽  
Collagen Gels ◽  
Human Bronchial Epithelial Cells ◽  
Maximal Contraction ◽  
Bronchial Epithelial ◽  
Contract Type

Fibroblasts can contract collagen gels, a process thought to be related to tissue remodeling. Because epithelial cells are also involved in repair responses, we postulated that human bronchial epithelial cells (HBECs) could cause contraction of collagen gels. To evaluate this, HBECs were plated on the top of native type I collagen gels and were incubated for 48 h. After this, the gels were released and floated in LHC-9-RPMI 1640 for varying times, and gel size was measured with an image analyzer. HBECs caused a marked contraction of the gels within 24 h; the area was reduced by 88 ± 4% ( P < 0.01). The degree of gel contraction was dependent on cell density; 12,500 cells/cm2 resulted in maximal contraction, and half-maximal contraction occurred at 7,500 cells/cm2. Contraction varied inversely with the collagen concentration (91 ± 1% with 0.5 mg/ml collagen vs. 43 ± 5% with 1.5 mg/ml collagen). In contrast to fibroblasts that contract gels most efficiently when cast into the gel, HBEC-mediated contraction was significantly ( P < 0.01) more efficient when cells were on top of the gels rather than when cast into the gels. Anti-β1-integrin antibody blocked HBEC-mediated contraction by >50%, whereas anti-α2-, anti-α3-, anti-αv-, anti-αvβ5-, anti-β2-, or anti-β4-integrin antibody was without effect. The combination of anti-β1-integrin antibody and an anti-α-subfamily antibody completely blocked gel contraction induced by HBECs. In contrast, anti-cellular fibronectin antibody did not block HBEC-induced gel contraction, whereas it did block fibroblast-mediated gel contraction. In summary, human airway epithelial cells can contract type I collagen gels, a process that appears to require integrins but may not require fibronectin. This process may contribute to airway remodeling.

scholarly journals Human coronaviruses 229E and OC43 replicate and induce distinct antiviral responses in differentiated primary human bronchial epithelial cells

2020 ◽  
Vol 319 (6) ◽  
pp. L926-L931
Author(s):  
Su-Ling Loo ◽  
Peter A. B. Wark ◽  
Camille Esneau ◽  
Kristy S. Nichol ◽  
Alan C-Y. Hsu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Time Course ◽  
Bronchial Epithelial Cells ◽  
Innate Immune ◽  
Infection Model ◽  
Type I ◽  
Human Bronchial Epithelial Cells ◽  
Cell Infection ◽  
Bronchial Epithelial ◽  
Human Coronaviruses

The recurrent emergence of novel, pathogenic coronaviruses (CoVs) severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; 2002), Middle East respiratory syndrome (MERS)-CoV (2012), and most recently SARS-CoV-2 (2019) has highlighted the need for physiologically informative airway epithelial cell infection models for studying immunity to CoVs and development of antiviral therapies. To address this, we developed an in vitro infection model for two human coronaviruses; alphacoronavirus 229E-CoV (229E) and betacoronavirus OC43-CoV (OC43) in differentiated primary human bronchial epithelial cells (pBECs). Primary BECs from healthy subjects were grown at air-liquid interface (ALI) and infected with 229E or OC43, and replication kinetics and time-course expression of innate immune mediators were assessed. OC43 and 229E-CoVs replicated in differentiated pBECs but displayed distinct replication kinetics: 229E replicated rapidly with viral load peaking at 24 h postinfection, while OC43 replication was slower peaking at 96 h after infection. This was associated with diverse antiviral response profiles defined by increased expression of type I/III interferons and interferon-stimulated genes (ISGs) by 229E compared with no innate immune activation with OC43 infection. Understanding the host-virus interaction for previously established coronaviruses will give insight into pathogenic mechanisms underpinning SARS-CoV-2-induced respiratory disease and other future coronaviruses that may arise from zoonotic sources.

Interleukin-10 Regulates Transforming Growth Factor-β Signaling in Cultured Human Bronchial Epithelial Cells

Respiration ◽  
2007 ◽  
Vol 74 (4) ◽  
pp. 454-459 ◽  
Author(s):  
Naoto Fueki ◽  
Hironori Sagara ◽  
Kazumi Akimoto ◽  
Mayumi Ota ◽  
Takenori Okada ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

Cell-matrix and cell-cell interactions modulate apoptosis of bronchial epithelial cells

1997 ◽  
Vol 272 (1) ◽  
pp. L28-L37 ◽  
Author(s):  
K. Aoshiba ◽  
S. I. Rennard ◽  
J. R. Spurzem
Keyword(s):  
Epithelial Cells ◽  
Type I Collagen ◽  
Bronchial Epithelium ◽  
Cell Aggregation ◽  
Cell Number ◽  
Bronchial Epithelial Cells ◽  
Cell Interactions ◽  
Type I ◽  
Bronchial Epithelial ◽  
Cell Cell

Apoptosis is an important process maintaining cell number and tissue structure. To determine whether cell-extracellular matrix (ECM) and cell-cell interactions modulate apoptosis in bronchial epithelium, we cultured human bronchial epithelial cells in different conditions and evaluated the cells for apoptosis. We found that plating cells in conditions that prevent cell-ECM adhesion induced apoptosis. Plating cells on type I collagen, fibronectin, and biosynthesized matrix prevented apoptosis, due at least in part to integrin-mediated adhesion. When cells were cultured at high density but under conditions preventing cell-substratum adhesion, aggregation occurred. Apoptosis was inversely correlated with aggregation. Cell-cell adhesion in these conditions was mediated at least partly by integrins containing alpha v. Cell aggregation was not associated with activation of a signaling pathway that is usually activated by cell-ECM adhesion, phosphorylation of focal adhesion kinase, but was associated with Bcl-2 protein expression, consistent with the concept that Bcl-2 protects against apoptosis. We conclude that both cell-ECM and cell-cell interactions, likely mediated in part by integrins, modulate apoptosis in bronchial epithelium.

scholarly journals Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β1 in epithelial-mesenchymal trophic unit model

2020 ◽  
Author(s):  
Milena Paw ◽  
Dawid Wnuk ◽  
Bogdan Jakieła ◽  
Grażyna Bochenek ◽  
Krzysztof Sładek ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Bronchial Epithelial Cells ◽  
Intrinsic Properties ◽  
Human Bronchial Epithelial Cells ◽  
High Concentration ◽  
Bronchial Epithelial ◽  
Mesenchymal Transition

Abstract Background: Asthma-related airway wall remodeling is associated with i.a. damage of bronchial epithelium and subepithelial fibrosis. Functional interactions between human bronchial epithelial cells and human bronchial fibroblasts are known as the epithelial-mesenchymal trophic unit (EMTU) and are necessary for a proper functioning of lung tissue. However, a high concentration of the transforming growth factor-β 1 (TGF-β 1 ) in the asthmatic bronchi drives the structural disintegrity of epithelium with the epithelial-to-mesenchymal transition (EMT) of the bronchial epithelial cells, and of subepitheial fibrosis with the fibroblast-to-myofibroblast transition (FMT) of the bronchial fibroblasts. Since previous reports indicate different intrinsic properties of the human bronchial epithelial cells and the human bronchial fibroblasts which affect their EMT/FMT potential beetween cells derived from asthmatic and non-asthmatic patients, cultured separatelly in vitro , we were interested to see whether corresponding effects could be obtained in co-cultures of bronchial epithelial cells and bronchial fibroblasts. In this study, we investigate the effects of the TGF-β 1 on the EMT markers of the bronchial epithelial cells cultured in the air-liquid-interface and effectiveness of FMT in the bronchial fibroblast populations in the EMTU models. Results: Our results show that the asthmatic co-cultures are more sensitive to the TGF-β 1 than the non-asthmatic ones, which is associated with a higher potential of asthmatic bronchial cells for a profibrotic response, analogously to be observed in “2D” cultures. Moreover, our results indicate a noticeable impact of human bronchial epithelial cells on the TGF-β 1 -induced FMT, stronger in the asthmatic bronchial fibroblast populations in comparison to the non-asthmatic ones. Conclusions: Our data are the first to demonstrate a protective effect of human bronchial fibroblasts on the properties of human bronchial epithelial cells, which suggests that intrinsic properties of not only epithelium but also subepithelial fibroblasts affect a proper condition and function of the EMTU in both normal and asthmatic individuals.

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