scholarly journals What Have In Vitro Co-Culture Models Taught Us about the Contribution of Epithelial-Mesenchymal Interactions to Airway Inflammation and Remodeling in Asthma?

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1694
Author(s):  
Emmanuel Twumasi Osei ◽  
Steven Booth ◽  
Tillie-Louise Hackett
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Airway Inflammation ◽  
Airway Epithelial ◽  
Disease Pathogenesis ◽  
3 Dimensional ◽  
Lung Epithelial ◽  
Culture Models

As the lung develops, epithelial-mesenchymal crosstalk is essential for the developmental processes that drive cell proliferation, differentiation, and extracellular matrix (ECM) production within the lung epithelial-mesenchymal trophic unit (EMTU). In asthma, a number of the lung EMTU developmental signals have been associated with airway inflammation and remodeling, which has led to the hypothesis that aberrant activation of the asthmatic EMTU may lead to disease pathogenesis. Monoculture studies have aided in the understanding of the altered phenotype of airway epithelial and mesenchymal cells and their contribution to the pathogenesis of asthma. However, 3-dimensional (3D) co-culture models are needed to enable the study of epithelial-mesenchymal crosstalk in the setting of the in vivo environment. In this review, we summarize studies using 3D co-culture models to assess how defective epithelial-mesenchymal communication contributes to chronic airway inflammation and remodeling within the asthmatic EMTU.

Proliferation and repair of guinea pig tracheal epithelium after neuropeptide depletion and injury in vivo

1997 ◽  
Vol 273 (6) ◽  
pp. L1235-L1241 ◽  
Author(s):  
John S. Kim ◽  
Valerie S. McKinnis ◽  
Kimberly Adams ◽  
Steven R. White
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mucosal Injury ◽  
Nuclear Antigen ◽  
Airway Epithelial ◽  
Epithelial Cell Proliferation ◽  
Injury Site ◽  
And Migration

Neuropeptides stimulate airway epithelial cell proliferation and migration in vitro, but the role of neuropeptides in the repair of the epithelium after injury in vivo is not clear. We studied epithelial proliferation and repair in 83 male Hartley guinea pigs. Animals received capsaicin weekly for 3 wk to deplete airway neuropeptides. One week later, the dorsal aspect of the trachea was injured with a metal stylette. Animals were killed 1 h to 1 wk later, after which epithelial cell proliferation was assessed for the presence of proliferating cell nuclear antigen (PCNA). PCNA labeling was <3% in noninjured animals. PCNA labeling increased substantially in the first 72 h after injury in control animals but was significantly decreased in capsaicin-treated animals within and adjacent to the site of injury. PCNA labeling increased opposite to the injury site in both control and capsaicin animals over the first 72 h. We conclude that neuropeptide depletion significantly attenuates both epithelial cell proliferation and repair in the first 72 h after mechanical injury to the trachea. However, neuropeptide depletion did not slow the ultimate repair of tracheal mucosal injury. Proliferation of epithelial cells in response to injury occurs throughout the airway, even away from the injury site.

scholarly journals Blockade of Airway Inflammation by Kaempferol via Disturbing Tyk-STAT Signaling in Airway Epithelial Cells and in Asthmatic Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ju-Hyun Gong ◽  
Daekeun Shin ◽  
Seon-Young Han ◽  
Sin-Hye Park ◽  
Min-Kyung Kang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Airway Inflammation ◽  
Airway Epithelium ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Bronchial Inflammation ◽  
Stat Signaling ◽  
Socs3 Expression

Asthma is characterized by bronchial inflammation causing increased airway hyperresponsiveness and eosinophilia. The interaction between airway epithelium and inflammatory mediators plays a key role in the asthmatic pathogenesis. Thein vitrostudy elucidated inhibitory effects of kaempferol, a flavonoid found in apples and many berries, on inflammation in human airway epithelial BEAS-2B cells. Nontoxic kaempferol at ≤20 μM suppressed the LPS-induced IL-8 production through the TLR4 activation, inhibiting eotaxin-1 induction. Thein vivostudy explored the demoting effects of kaempferol on asthmatic inflammation in BALB/c mice sensitized with ovalbumin (OVA). Mouse macrophage inflammatory protein-2 production and CXCR2 expression were upregulated in OVA-challenged mice, which was attenuated by oral administration of ≥10 mg/kg kaempferol. Kaempferol allayed the airway tissue levels of eotaxin-1 and eotaxin receptor CCR3 enhanced by OVA challenge. This study further explored the blockade of Tyk-STAT signaling by kaempferol in both LPS-stimulated BEAS-2B cells and OVA-challenged mice. LPS activated Tyk2 responsible for eotaxin-1 induction, while kaempferol dose-dependently inhibited LPS- or IL-8-inflamed Tyk2 activation. Similar inhibition of Tyk2 activation by kaempferol was observed in OVA-induced mice. Additionally, LPS stimulated the activation of STAT1/3 signaling concomitant with downregulated expression of Tyk-inhibiting SOCS3. In contrast, kaempferol encumbered STAT1/3 signaling with restoration of SOCS3 expression. Consistently, oral administration of kaempferol blocked STAT3 transactivation elevated by OVA challenge. These results demonstrate that kaempferol alleviated airway inflammation through modulating Tyk2-STAT1/3 signaling responsive to IL-8 in endotoxin-exposed airway epithelium and in asthmatic mice. Therefore, kaempferol may be a therapeutic agent targeting asthmatic diseases.

scholarly journals Airway Epithelial Cell Migration Dynamics: MMP-9 Role in Cell–Extracellular Matrix Remodeling

1999 ◽  
Vol 146 (2) ◽  
pp. 517-529 ◽  
Author(s):  
Claire Legrand ◽  
Christine Gilles ◽  
Jean-Marie Zahm ◽  
Myriam Polette ◽  
Anne-Cécile Buisson ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Leading Edge ◽  
Collagen Iv ◽  
Matrix Remodeling ◽  
Airway Epithelial ◽  
Type Iv ◽  
Migration Dynamics

Cell spreading and migration associated with the expression of the 92-kD gelatinase (matrix metalloproteinase 9 or MMP-9) are important mechanisms involved in the repair of the respiratory epithelium. We investigated the location of MMP-9 and its potential role in migrating human bronchial epithelial cells (HBEC). In vivo and in vitro, MMP-9 accumulated in migrating HBEC located at the leading edge of a wound and MMP-9 expression paralleled cell migration speed. MMP-9 accumulated through an actin-dependent pathway in the advancing lamellipodia of migrating cells and was subsequently found active in the extracellular matrix (ECM). Lamellipodia became anchored through primordial contacts established with type IV collagen. MMP-9 became amassed behind collagen IV where there were fewer cell–ECM contacts. Both collagen IV and MMP-9 were involved in cell migration because when cell–collagen IV interaction was blocked, cells spread slightly but did not migrate; and when MMP-9 activation was prevented, cells remained fixed on primordial contacts and did not advance at all. These observations suggest that MMP-9 controls the migration of repairing HBEC by remodeling the provisional ECM implicated in primordial contacts.

scholarly journals Susceptibility for cigarette smoke-induced DAMP release and DAMP-induced inflammation in COPD

2016 ◽  
Vol 311 (5) ◽  
pp. L881-L892 ◽  
Author(s):  
Simon D. Pouwels ◽  
Laura Hesse ◽  
Alen Faiz ◽  
Jaap Lubbers ◽  
Priya K. Bodha ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Gene Set Enrichment Analysis ◽  
Gene Profiling ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Copd Patients ◽  
Galectin 3

Cigarette smoke (CS) exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). We investigated whether CS-induced damage-associated molecular pattern (DAMP) release or DAMP-mediated inflammation contributes to susceptibility for COPD. Samples, including bronchial brushings, were collected from young and old individuals, susceptible and nonsusceptible for the development of COPD, before and after smoking, and used for gene profiling and airway epithelial cell (AEC) culture. AECs were exposed to CS extract (CSE) or specific DAMPs. BALB/cByJ and DBA/2J mice were intranasally exposed to LL-37 and mitochondrial (mt)DAMPs. Functional gene-set enrichment analysis showed that CS significantly increases the airway epithelial gene expression of DAMPs and DAMP receptors in COPD patients. In cultured AECs, we observed that CSE induces necrosis and DAMP release, with specifically higher galectin-3 release from COPD-derived compared with control-derived cells. Galectin-3, LL-37, and mtDAMPs increased CXCL8 secretion in AECs. LL-37 and mtDAMPs induced neutrophilic airway inflammation, exclusively in mice susceptible for CS-induced airway inflammation. Collectively, we show that in airway epithelium from COPD patients, the CS-induced expression of DAMPs and DAMP receptors in vivo and the release of galectin-3 in vitro is exaggerated. Furthermore, our studies indicate that a predisposition to release DAMPs and subsequent induction of inflammation may contribute to the development of COPD.

Factors Controlling Movement of Skeletal Muscles

Leonardo ◽  
2015 ◽  
Vol 48 (3) ◽  
pp. 270-271
Author(s):  
Miranda D. Grounds
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Cell Membrane ◽  
Skeletal Muscles ◽  
Muscle Cells ◽  
The Body ◽  
Skeletal Muscle Cells ◽  
3 Dimensional

The contraction of specialized skeletal muscle cells results in classic movements of bones and other parts of the body that are vital for life. There is exquisite control over the movement of diverse types of muscles. This paper indicates the way in which skeletal muscles (myofibres) are formed; then factors that contribute to generating the movement are outlined: these include the nerve, sarcomeres, cytoskeleton, cell membrane and the extracellular matrix. The factors controlling the movement of mature myofibres in 3-dimensional tissues in vivo are vastly more complex than for tissue cultured immature muscle cells in an artificial in vitro environment.

17,18-Epoxyeicosatetraenoic Acid Inhibits TNF-α-Induced Inflammation in Cultured Human Airway Epithelium and LPS-Induced Murine Airway Inflammation

2021 ◽  
pp. 194589242110276
Author(s):  
Shiori Hara ◽  
Ichiro Tojima ◽  
Shino Shimizu ◽  
Hideaki Kouzaki ◽  
Takeshi Shimizu
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Neutrophil Infiltration ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Mucus Production ◽  
Chemokine Production ◽  
In Vivo Effects

Background 17,18-Epoxyeicosatetraenoic acid (17,18-EpETE), an eicosapentaenoic acid metabolite, is generated from dietary oil in the gut, and antiinflammatory activity of 17,18-EpETE was recently reported. Objective To evaluate the inhibitory effects of 17,18-EpETE in airway inflammation, we examined in vitro and in vivo effects on mucus production, neutrophil infiltration, and cytokine/chemokine production in airway epithelium. Methods Nasal tissue localization of G protein-coupled receptor 40 (GPR40), a receptor of 17,18-EpETE, was determined by immunohistochemical staining. Expression of GPR40 mRNA in nasal mucosa of chronic rhinosinusitis (CRS) patients and control subjects was determined by reverse transcription-polymerase chain reaction (RT-PCR). The in vitro effects on airway epithelial cells were examined using normal human bronchial epithelial cells and NCI-H292 cells. To examine the in vivo effects of 17,18-EpETE on airway inflammation, we induced goblet cell metaplasia, mucus production, and neutrophil infiltration in mouse nasal epithelium by intranasal lipopolysaccharide (LPS) instillation. Results GPR40 is mainly expressed in human nasal epithelial cells and submucosal gland cells. RT-PCR analysis revealed that the expression of GPR40 mRNA was increased in nasal tissues from CRS patients compared with those from control subjects. 17,18-EpETE significantly inhibited tumor necrosis factor (TNF)-α-induced production of interleukin (IL)-6 , IL-8, and mucin from cultured human airway epithelial cells dose dependently, and these antiinflammatory effects on cytokine production were abolished by GW1100, a selective GPR40 antagonist. Intraperitoneal injection or intranasal instillation of 17,18-EpETE significantly attenuated LPS-induced mucus production and neutrophil infiltration in mouse nasal epithelium. Inflammatory cytokine/chemokine production in lung tissues and bronchoalveolar lavage fluids was also inhibited. Conclusion These results indicate that 17,18-EpETE plays a regulatory role in mucus hypersecretion and neutrophil infiltration in nasal inflammation. Local or systemic administration may provide a new therapeutic approach for the treatment of intractable airway disease such as CRS.

Extracellular matrix extraction techniques and applications in biomedical engineering

2021 ◽  
Vol 16 (8) ◽  
pp. 775-802
Author(s):  
Kirthanashri S Vasanthan ◽  
Varadharajan Srinivasan ◽  
Deepti Pandita
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Biomedical Applications ◽  
Tissue Formation ◽  
Drug Delivery Vehicles ◽  
Organ Regeneration ◽  
Detailed Assessment ◽  
Delivery Vehicles

The concept of tissue engineering involves regeneration and repair of damaged tissue and organs using various combinations of cells, growth factors and scaffolds. The extracellular matrix (ECM) forms the integral part of the scaffold to induce cell proliferation thereby leading to new tissue formation. Decellularization technique provides decellularized ECM (dECM), free of cells while preserving the in vivo biomolecules. In this review, we focus on the detailed methodology of diverse decellularization techniques for various organs of different animals, and the biomedical applications employing the dECM. A culmination of different methods of decellularization is optimized, which offers a suitable microenvironment mimicking the native in vivo topography for in vitro organ regeneration. A detailed assessment of the dECM provides information on the microarchitecture, presence of ECM proteins, biocompatibility and cell proliferation. dECM has also been processed as scaffolds and drug-delivery vehicles, and utilized for regeneration.

Development of an injectable thiolated icariin functionalized collagen/hyaluronic hydrogel to promote cartilage formation in vitro and in vivo

2019 ◽  
Vol 7 (17) ◽  
pp. 2845-2854 ◽  
Author(s):  
Yanbo Liu ◽  
Jirong Yang ◽  
Zhaocong Luo ◽  
Dongxiao Li ◽  
Jian Lu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Hyaluronic Acid ◽  
Chondrocyte Phenotype ◽  
Cartilage Formation ◽  
Physiological Conditions ◽  
Collagen Hydrogel ◽  
Cartilage Extracellular Matrix

We have developed an injectable thiolated icariin functionalized hyaluronic acid/collagen hydrogel under physiological conditions to facilitate cell proliferation, maintain chondrocyte phenotype and promote the secretion of the cartilage extracellular matrix.

scholarly journals Early Reduction of SARS-CoV-2 Replication in Bronchial Epithelium by Kinin B2 Receptor Antagonism

2021 ◽  
Author(s):  
Constanze A. Jakwerth ◽  
Martin Feuerherd ◽  
Ferdinand M. Guerth ◽  
Madlen Oelsner ◽  
Linda Schellhammer ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Early Stage ◽  
Bronchial Epithelium ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Inflammation Model ◽  
Protection Potential

Background: SARS-CoV2 has evolved to enter the host via the ACE2 receptor which is part of the Kinin-kallirein pathway. This complex pathway is only poorly understood in context of immune regulation but critical to control infection. This study examines SARS-CoV2 infection and epithelial mechanisms of the kinin-kallikrein system at the kinin B2 receptor level in SARS-CoV-2 infection that is of direct translational relevance. Methods: From acute SARS-CoV-2-positive patients and -negative controls, transcriptomes of nasal brushings were analyzed. Primary airway epithelial cells (NHBEs) were infected with SARS-CoV-2 and treated with the approved B2R antagonist icatibant. SARS-CoV-2 RNA RT-qPCR, cytotoxicity assays, plaque assays and transcriptome analyses were performed. The treatment effect was further studied in a murine airway inflammation model in vivo. Results: Here, we report a broad and strong upregulation of kallikreins and the kinin B2 receptor (B2R) in the nasal mucosa of acutely symptomatic SARS-CoV-2-positive patients. A B2R antagonist impeded SARS-CoV-2 replication and spread in NHBEs, as determined in plaque assays on Vero E6 cells. B2R antagonism reduced the expression of SARS-CoV-2 entry receptor ACE2 in vitro and in a murine airway inflammation model in vivo. In addition, it suppressed gene expression broadly, particularly genes involved in G-protein-coupled-receptor signaling and ion transport. Conclusions: In summary, this study provides evidence that treatment with B2R antagonists protects airway epithelial cells from SARS-CoV-2 by inhibiting its replication and spread, through the reduction of ACE2 levels and the interference with several cellular signaling processes. Future clinical studies need to shed light on the airway protection potential of approved B2R antagonists, like icatibant, in the treatment of early-stage COVID-19.

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