scholarly journals Silica Nanoparticles Inhibit Responses to ATP in Human Airway Epithelial 16HBE Cells

2021 ◽  
Vol 22 (18) ◽  
pp. 10173
Author(s):  
Alina Milici ◽  
Alicia Sanchez ◽  
Karel Talavera
Keyword(s):  
Silica Nanoparticles ◽  
Inflammatory Responses ◽  
Low Cost ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Molecular Pattern ◽  
Competitive Mechanism ◽  
Exposure Levels ◽  
Manufacturing Applications

Because of their low cost and easy production, silica nanoparticles (SiNPs) are widely used in multiple manufacturing applications as anti-caking, densifying and hydrophobic agents. However, this has increased the exposure levels of the general population and has raised concerns about the toxicity of this nanomaterial. SiNPs affect the function of the airway epithelium, but the biochemical pathways targeted by these particles remain largely unknown. Here we investigated the effects of SiNPs on the responses of 16HBE14o- cultured human bronchial epithelial (16HBE) cells to the damage-associated molecular pattern ATP, using fluorometric measurements of intracellular Ca2+ concentration. Upon stimulation with extracellular ATP, these cells displayed a concentration-dependent increase in intracellular Ca2+, which was mediated by release from intracellular stores. SiNPs inhibited the Ca2+ responses to ATP within minutes of application and at low micromolar concentrations, which are significantly faster and more potent than those previously reported for the induction of cellular toxicity and pro-inflammatory responses. SiNPs-induced inhibition is independent from the increase in intracellular Ca2+ they produce, is largely irreversible and occurs via a non-competitive mechanism. These findings suggest that SiNPs reduce the ability of airway epithelial cells to mount ATP-dependent protective responses.

scholarly journals Silica Nanoparticles Inhibit ATP Responses of Human Airway Epithelial 16HBE Cells

2021 ◽  
Author(s):  
Alina Milici ◽  
Alicia Sanchez ◽  
Karel Talavera
Keyword(s):  
Silica Nanoparticles ◽  
Mucociliary Clearance ◽  
Inflammatory Responses ◽  
Low Cost ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Molecular Pattern ◽  
Competitive Mechanism ◽  
Exposure Levels

Because of their low cost and easy production silica nanoparticles (NPs) are amply used in multiple manufactures as anti-caking, densifying and hydrophobic agents. However, this has increased the exposure levels of the general population and has raised concerns about possible toxicity of this nanomaterial. NPs are known to affect the function of the airway epithelium, but the biochemical pathways targeted by these particles remain largely unknown. Here we investigated the effects of NPs on the responses of cultured human bronchial epithelial (16HBE) cells to the damage-associated molecular pattern ATP, using fluorometric measurements of intracellular Ca2+ concentration. Upon stimulation with extracellular ATP these cells displayed a concentration-dependent increase in intracellular Ca2+, which was mediated by release from intracellular stores. Silica NPs inhibited the Ca2+ responses to ATP within minutes of application and at low micromolar concentrations, which are significantly faster and more potent than those previously reported for the induction of cellular toxicity and pro-inflammatory responses. NPs-induced inhibition appeared to be independent from the increase in intracellular Ca2+ they produce, and via a non-competitive mechanism. These findings suggest that NPs reduce the ability of airway epithelial cells to mount ATP-dependent protective responses such as the increase in mucociliary clearance and cough.

scholarly journals Capsular Polysaccharide is a Main Component ofMycoplasma ovipneumoniaein the Pathogen-Induced Toll-Like Receptor-Mediated Inflammatory Responses in Sheep Airway Epithelial Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Zhongjia Jiang ◽  
Fuyang Song ◽  
Yanan Li ◽  
Di Xue ◽  
Guangcun Deng ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Capsular Polysaccharide ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Atypical Pneumonia ◽  
Activator Protein 1 ◽  
Airway Epithelial ◽  
Toll Like Receptor ◽  
Bronchial Epithelial

Mycoplasma ovipneumoniae(M. ovipneumoniae) is characterized as an etiological agent of primary atypical pneumonia that specifically infects sheep and goat. In an attempt to better understand the pathogen-host interaction between the invadingM. ovipneumoniaeand airway epithelial cells, we investigated the host inflammatory responses against capsular polysaccharide (designated as CPS) ofM. ovipneumoniaeusing sheep bronchial epithelial cells cultured in an air-liquid interface (ALI) model. Results showed that CPS derived fromM. ovipneumoniaecould activate toll-like receptor- (TLR-) mediated inflammatory responses, along with an elevated expression of nuclear factor kappa B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factor 3 (IRF3) as well as various inflammatory-associated mediators, representatively including proinflammatory cytokines, such as IL1β, TNFα, and IL8, and anti-inflammatory cytokines such as IL10 and TGFβof TLR signaling cascade. Mechanistically, the CPS-induced inflammation was TLR initiated and was mediated by activations of both MyD88-dependent and MyD88-independent signaling pathways. Of importance, a blockage of CPS with specific antibody led a significant reduction ofM. ovipneumoniae-induced inflammatory responses in sheep bronchial epithelial cells. These results suggested that CPS is a key virulent component ofM. ovipneumoniae, which may play a crucial role in the inflammatory response induced byM. ovipneumoniaeinfections.

ICAM-1-independent adhesion of neutrophils to phorbol ester-stimulated human airway epithelial cells

1999 ◽  
Vol 277 (3) ◽  
pp. L465-L471 ◽  
Author(s):  
Alessandro Celi ◽  
Silvana Cianchetti ◽  
Stefano Petruzzelli ◽  
Stefano Carnevali ◽  
Filomena Baliva ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Neutrophil Adhesion ◽  
Late Time ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Human Airway ◽  
Stimulation Of ◽  
Human Airway Epithelial Cells

Intercellular adhesion molecule-1 (ICAM-1) is the only inducible adhesion receptor for neutrophils identified in bronchial epithelial cells. We stimulated human airway epithelial cells with various agonists to evaluate whether ICAM-1-independent adhesion mechanisms could be elicited. Phorbol 12-myristate 13-acetate (PMA) stimulation of cells of the alveolar cell line A549 caused a rapid, significant increase in neutrophil adhesion from 11 ± 3 to 49 ± 7% (SE). A significant increase from 17 ± 4 to 39 ± 6% was also observed for neutrophil adhesion to PMA-stimulated human bronchial epithelial cells in primary culture. Although ICAM-1 expression was upregulated by PMA at late time points, it was not affected at 10 min when neutrophil adhesion was already clearly enhanced. Antibodies to ICAM-1 had no effect on neutrophil adhesion. In contrast, antibodies to the leukocyte integrin β-chain CD18 totally inhibited the adhesion of neutrophils to PMA-stimulated epithelial cells. These results demonstrate that PMA stimulation of human airway epithelial cells causes an increase in neutrophil adhesion that is not dependent on ICAM-1 upregulation.

scholarly journals Overproduction of growth differentiation factor 15 promotes human rhinovirus infection and virus-induced inflammation in the lung

2018 ◽  
Vol 314 (3) ◽  
pp. L514-L527 ◽  
Author(s):  
Qun Wu ◽  
Di Jiang ◽  
Niccolette R. Schaefer ◽  
Laura Harmacek ◽  
Brian P. O’Connor ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Human Rhinovirus ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Growth Differentiation Factor 15 ◽  
Human Airway ◽  
Differentiation Factor ◽  
Human Airway Epithelial Cells

Human rhinovirus (HRV) is the most common virus contributing to acute exacerbations of chronic obstructive pulmonary disease (COPD) nearly year round, but the mechanisms have not been well elucidated. Recent clinical studies suggest that high levels of growth differentiation factor 15 (GDF15) protein in the blood are associated with an increased yearly rate of all-cause COPD exacerbations. Therefore, in the current study, we investigated whether GDF15 promotes HRV infection and virus-induced lung inflammation. We first examined the role of GDF15 in regulating host defense and HRV-induced inflammation using human GDF15 transgenic mice and cultured human GDF15 transgenic mouse tracheal epithelial cells. Next, we determined the effect of GDF15 on viral replication, antiviral responses, and inflammation in human airway epithelial cells with GDF15 knockdown and HRV infection. Finally, we explored the signaling pathways involved in airway epithelial responses to HRV infection in the context of GDF15. Human GDF15 protein overexpression in mice led to exaggerated inflammatory responses to HRV, increased infectious particle release, and decreased IFN-λ2/3 (IL-28A/B) mRNA expression in the lung. Moreover, GDF15 facilitated HRV replication and inflammation via inhibiting IFN-λ1/IL-29 protein production in human airway epithelial cells. Lastly, Smad1 cooperated with interferon regulatory factor 7 (IRF7) to regulate airway epithelial responses to HRV infection partly via GDF15 signaling. Our results reveal a novel function of GDF15 in promoting lung HRV infection and virus-induced inflammation, which may be a new mechanism for the increased susceptibility and severity of respiratory viral (i.e., HRV) infection in cigarette smoke-exposed airways with GDF15 overproduction.

Resting and Cytokine-Stimulated Human Small Airway Epithelial Cells Recognize and Engulf Apoptotic Eosinophils

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2827-2835 ◽  
Author(s):  
Garry M. Walsh ◽  
Darren W. Sexton ◽  
Morgan G. Blaylock ◽  
Catherine M. Convery
Keyword(s):  
Epithelial Cells ◽  
Interleukin 1 ◽  
Airway Epithelial Cells ◽  
Small Airway ◽  
Airway Epithelial ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Small Airway Epithelial Cells ◽  
Necrosis Factor

Eosinophils, which are prominent cells in asthmatic inflammation, undergo apoptosis and are recognized and engulfed by phagocytic macrophages in vitro. We have examined the ability of human small airway epithelial cells (SAEC) to recognize and ingest apoptotic human eosinophils. Cultured SAEC ingested apoptotic eosinophils but not freshly isolated eosinophils or opsonized erythrocytes. The ability of SAEC to ingest apoptotic eosinophils was enhanced by interleukin-1 (IL-1) or tumor necrosis factor  (TNF) in a time- and concentration-dependent fashion. IL-1 was found to be more potent than TNF and each was optimal at 10−10 mol/L, with a significant (P < .05) effect observed at 1 hour postcytokine incubation that was maximal at 5 hours. IL-1 stimulation not only increased the number of SAEC engulfing apoptotic eosinophils, but also enhanced their capacity for ingestion. The amino sugars glucosamine, n-acetyl glucosamine, and galactosamine significantly inhibited uptake of apoptotic eosinophils by both resting and IL-1–stimulated SAEC, in contrast to the parent sugars glucose, galactose, mannose, and fucose. Incubation of apoptotic eosinophils with the tetrapeptide RGDS, but not RGES, significantly inhibited their uptake by both resting and IL-1–stimulated SAEC, as did monoclonal antibody against vβ3 and CD36. Thus, SAEC recognize apoptotic eosinophils via lectin- and integrin-dependent mechanisms. These data demonstrate a novel function for human bronchial epithelial cells that might represent an important mechanism in the resolution of eosinophil-induced asthmatic inflammation.

Innate Inflammatory Responses of Pediatric Cystic Fibrosis Airway Epithelial Cells

2011 ◽  
Vol 44 (6) ◽  
pp. 761-767 ◽  
Author(s):  
Erika N. Sutanto ◽  
Anthony Kicic ◽  
Clara J. Foo ◽  
Paul T. Stevens ◽  
David Mullane ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Cystic Fibrosis Airway

scholarly journals Streamer discharge reduces pollen-induced inflammatory responses and injury in human airway epithelial cells

2013 ◽  
Vol 238 (2) ◽  
pp. 187-192
Author(s):  
Akiko Honda ◽  
Rumiko Murayama ◽  
Kenshi Tsuji ◽  
Yugo Matsuda ◽  
Eiko Koike ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Streamer Discharge ◽  
Human Airway ◽  
Human Airway Epithelial Cells

scholarly journals Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells

2012 ◽  
Vol 303 (2) ◽  
pp. L97-L106 ◽  
Author(s):  
Shilpa Nimishakavi ◽  
Marina Besprozvannaya ◽  
Wilfred W. Raymond ◽  
Charles S. Craik ◽  
Dieter C. Gruenert ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Cell Surface ◽  
Selective Inhibition ◽  
Airway Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Apical Surface ◽  
Airway Epithelial ◽  
Wild Type ◽  
Bronchial Epithelial

Prostasin is a membrane-anchored protease expressed in airway epithelium, where it stimulates salt and water uptake by cleaving the epithelial Na+ channel (ENaC). Prostasin is activated by another transmembrane tryptic protease, matriptase. Because ENaC-mediated dehydration contributes to cystic fibrosis (CF), prostasin and matriptase are potential therapeutic targets, but their catalytic competence on airway epithelial surfaces has been unclear. Seeking tools for exploring sites and modulation of activity, we used recombinant prostasin and matriptase to identify substrate t-butyloxycarbonyl-l-Gln-Ala-Arg-4-nitroanilide (QAR-4NA), which allowed direct assay of proteases in living cells. Comparisons of bronchial epithelial cells (CFBE41o−) with and without functioning cystic fibrosis transmembrane conductance regulator (CFTR) revealed similar levels of apical and basolateral aprotinin-inhibitable activity. Although recombinant matriptase was more active than prostasin in hydrolyzing QAR-4NA, cell surface activity resisted matriptase-selective inhibition, suggesting that prostasin dominates. Surface biotinylation revealed similar expression of matriptase and prostasin in epithelial cells expressing wild-type vs. ΔF508-mutated CFTR. However, the ratio of mature to inactive proprostasin suggested surface enrichment of active enzyme. Although small amounts of matriptase and prostasin were shed spontaneously, prostasin anchored to the cell surface by glycosylphosphatidylinositol was the major contributor to observed QAR-4NA-hydrolyzing activity. For example, the apical surface of wild-type CFBE41o− epithelial cells express 22% of total, extractable, aprotinin-inhibitable, QAR-4NA-hydrolyzing activity and 16% of prostasin immunoreactivity. In conclusion, prostasin is present, mature and active on the apical surface of wild-type and CF bronchial epithelial cells, where it can be targeted for inhibition via the airway lumen.

scholarly journals Cultured Human Airway Epithelial Cells (Calu-3): A Model of Human Respiratory Function, Structure, and Inflammatory Responses

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Yan Zhu ◽  
Aaron Chidekel ◽  
Thomas H. Shaffer
Keyword(s):  
Epithelial Cells ◽  
Cellular Response ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Treatment Modalities ◽  
Positive Pressure ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

This article reviews the application of the human airway Calu-3 cell line as a respiratory model for studying the effects of gas concentrations, exposure time, biophysical stress, and biological agents on human airway epithelial cells. Calu-3 cells are grown to confluence at an air-liquid interface on permeable supports. To model human respiratory conditions and treatment modalities, monolayers are placed in an environmental chamber, and exposed to specific levels of oxygen or other therapeutic modalities such as positive pressure and medications to assess the effect of interventions on inflammatory mediators, immunologic proteins, and antibacterial outcomes. Monolayer integrity and permeability and cell histology and viability also measure cellular response to therapeutic interventions. Calu-3 cells exposed to graded oxygen concentrations demonstrate cell dysfunction and inflammation in a dose-dependent manner. Modeling positive airway pressure reveals that pressure may exert a greater injurious effect and cytokine response than oxygen. In experiments with pharmacological agents, Lucinactant is protective of Calu-3 cells compared with Beractant and control, and perfluorocarbons also protect against hyperoxia-induced airway epithelial cell injury. The Calu-3 cell preparation is a sensitive and efficient preclinical model to study human respiratory processes and diseases related to oxygen- and ventilator-induced lung injury.

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