The Expression Profile of Protease Inhibitors in the Airway Epithelial Cells after Allergen (Der p 1) Stimulation

2021 ◽  
pp. 1-9
Author(s):  
Cagatay Karaaslan ◽  
Dilara Karaguzel ◽  
Basak Ezgi Sarac ◽  
Ceren Sucularli ◽  
Hayriye Akel Bilgic ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Protease Activity ◽  
Airway Epithelial Cells ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Time Points ◽  
Der P 1

<b><i>Background:</i></b> Airway epithelial cells are constantly exposed to intracellular and extracellular proteases that play a pivotal role in several airway diseases. <i>Dermatophagoides pteronyssinus</i> (Der p) 1 derived from house dust mite has protease activity that causes epithelial barrier defect and inflammatory response. Protease inhibitors released against proteases are involved in the maintenance of homeostasis. A disruption of the balance between proteases and protease inhibitors can lead to distortion of the cellular structures and cellular activities and thus culminate in disease processes. Although the effects of Der p 1 allergen on epithelial barrier integrity and inflammatory response are well-established, its contribution to protease inhibitor production is highly limited. <b><i>Objective:</i></b> This study aimed to determine the profile of the protease inhibitor response to Der p 1 allergen in human airway epithelial cells, A549 and BEAS-2B. <b><i>Methods:</i></b> Differentiated cells by the air-liquid interface were exposed to Der p 1 with or without Th2 type cytokines (IL-4 and IL-13). Gene expression of protease inhibitors was determined by qPCR at 2 different time points. <b><i>Results:</i></b> We found that the effect of allergen exposure on the protease inhibitor profile can vary depending on the antigen concentration, treatment duration, and the presence or absence of type 2 cytokines. Gene expressions of serine protease inhibitor (<i>SERPIN</i>)<i>B3</i> and <i>SERPINB4</i> were increased following Th2 cytokine stimulation in both cell types at both time points, whereas <i>SERPINB2</i> and <i>TFPI-2</i> expressions were induced by 24-h Der p 1 stimulation in both cells. <b><i>Conclusions:</i></b> Our study suggests that Der p 1 exposure of the airway epithelium may have consequences related to its protease activity in the presence as well as in the absence of Th2 cytokines in the microenvironment.

scholarly journals Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 509 ◽  
Author(s):  
Meenakshi Tiwary ◽  
Robert J. Rooney ◽  
Swantje Liedmann ◽  
Kim S. LeMessurier ◽  
Amali E. Samarasinghe
Keyword(s):  
Epithelial Cells ◽  
Influenza A Virus ◽  
Early Phase ◽  
Influenza A ◽  
Airway Epithelial Cells ◽  
Epithelial Barrier ◽  
Virus Infectivity ◽  
Airway Epithelial ◽  
In Vivo Models

Eosinophils, previously considered terminally differentiated effector cells, have multifaceted functions in tissues. We previously found that allergic mice with eosinophil-rich inflammation were protected from severe influenza and discovered specialized antiviral effector functions for eosinophils including promoting cellular immunity during influenza. In this study, we hypothesized that eosinophil responses during the early phase of influenza contribute to host protection. Using in vitro and in vivo models, we found that eosinophils were rapidly and dynamically regulated upon influenza A virus (IAV) exposure to gain migratory capabilities to traffic to lymphoid organs after pulmonary infection. Eosinophils were capable of neutralizing virus upon contact and combinations of eosinophil granule proteins reduced virus infectivity through hemagglutinin inactivation. Bi-directional crosstalk between IAV-exposed epithelial cells and eosinophils occurred after IAV infection and cross-regulation promoted barrier responses to improve antiviral defenses in airway epithelial cells. Direct interactions between eosinophils and airway epithelial cells after IAV infection prevented virus-induced cytopathology in airway epithelial cells in vitro, and eosinophil recipient IAV-infected mice also maintained normal airway epithelial cell morphology. Our data suggest that eosinophils are important in the early phase of IAV infection providing immediate protection to the epithelial barrier until adaptive immune responses are deployed during influenza.

scholarly journals Anti-Inflammatory Properties of Fructo-Oligosaccharides in a Calf Lung Infection Model and in Mannheimia haemolytica-Infected Airway Epithelial Cells

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3514
Author(s):  
Yang Cai ◽  
Myrthe S. Gilbert ◽  
Walter J. J. Gerrits ◽  
Gert Folkerts ◽  
Saskia Braber
Keyword(s):  
Epithelial Cells ◽  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Mannheimia Haemolytica ◽  
Epithelial Barrier ◽  
Infection Model ◽  
Airway Epithelial ◽  
Clinical Scores ◽  
Lung Infections ◽  
Anti Inflammatory

Emerging antimicrobial-resistant pathogens highlight the importance of developing novel interventions. Here, we investigated the anti-inflammatory properties of Fructo-oligosaccharides (FOS) in calf lung infections and in airway epithelial cells stimulated with pathogens, and/or bacterial components. During a natural exposure, 100 male calves were fed milk replacer with or without FOS for 8 weeks. Then, immune parameters and cytokine/chemokine levels in the bronchoalveolar lavage fluid (BALF) and blood were measured, and clinical scores were investigated. Calf primary bronchial epithelial cells (PBECs) and human airway epithelial cells (A549) were treated with Mannheimia haemolytica, lipopolysaccharides (LPS), and/or flagellin, with or without FOS pretreatment. Thereafter, the cytokine/chemokine levels and epithelial barrier function were examined. Relative to the control (naturally occurring lung infections), FOS-fed calves had greater macrophage numbers in BALF and lower interleukin (IL)-8, IL-6, and IL-1β concentrations in the BALF and blood. However, FOS did not affect the clinical scores. At slaughter, FOS-fed calves had a lower severity of lung lesions compared to the control. Ex vivo, FOS prevented M. haemolytica-induced epithelial barrier dysfunction. Moreover, FOS reduced M. haemolytica- and flagellin-induced (but not LPS-induced) IL-8, TNF-α, and IL-6 release in PBECs and A549 cells. Overall, FOS had anti-inflammatory properties during the natural incidence of lung infections but had no effects on clinical symptoms.

scholarly journals Induction of Mucin and MUC5AC Expression by the Protease Activity ofAspergillus fumigatusin Airway Epithelial Cells

2011 ◽  
Vol 187 (2) ◽  
pp. 999-1005 ◽  
Author(s):  
Tsuyoshi Oguma ◽  
Koichiro Asano ◽  
Katsuyoshi Tomomatsu ◽  
Motohiro Kodama ◽  
Koichi Fukunaga ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Protease Activity ◽  
Airway Epithelial Cells ◽  
Airway Epithelial

scholarly journals Connectivity mapping (ssCMap) to predict A20-inducing drugs and their antiinflammatory action in cystic fibrosis

2016 ◽  
Vol 113 (26) ◽  
pp. E3725-E3734 ◽  
Author(s):  
Beth Malcomson ◽  
Hollie Wilson ◽  
Eleonora Veglia ◽  
Gayathri Thillaiyampalam ◽  
Ruth Barsden ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Gene Array ◽  
Unmet Need ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Antiinflammatory Action ◽  
Functional Defect ◽  
Recent Developments

Cystic fibrosis (CF) lung disease is characterized by chronic and exaggerated inflammation in the airways. Despite recent developments to therapeutically overcome the underlying functional defect in the cystic fibrosis transmembrane conductance regulator, there is still an unmet need to also normalize the inflammatory response. The prolonged and heightened inflammatory response in CF is, in part, mediated by a lack of intrinsic down-regulation of the proinflammatory NF-κB pathway. We have previously identified reduced expression of the NF-κB down-regulator A20 in CF as a key target to normalize the inflammatory response. Here, we have used publicly available gene array expression data together with a statistically significant connections’ map (sscMap) to successfully predict drugs already licensed for the use in humans to induce A20 mRNA and protein expression and thereby reduce inflammation. The effect of the predicted drugs on A20 and NF-κB(p65) expression (mRNA) as well as proinflammatory cytokine release (IL-8) in the presence and absence of bacterial LPS was shown in bronchial epithelial cells lines (16HBE14o−, CFBE41o−) and in primary nasal epithelial cells from patients with CF (Phe508del homozygous) and non-CF controls. Additionally, the specificity of the drug action on A20 was confirmed using cell lines with tnfαip3 (A20) knockdown (siRNA). We also show that the A20-inducing effect of ikarugamycin and quercetin is lower in CF-derived airway epithelial cells than in non-CF cells.

scholarly journals Microbial interaction: Prevotella spp. reduce P.aeruginosa induced inflammation in Cystic Fibrosis bronchial epithelial cells

2020 ◽  
Author(s):  
Anne Bertelsen ◽  
Stuart J Elborn ◽  
Bettina Schock
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Bacterial Species ◽  
Airway Epithelial Cells ◽  
Lung Damage ◽  
Airway Epithelial ◽  
Lung Function Decline ◽  
Mapk Signalling ◽  
Microbial Environment

Abstract Background: In Cystic Fibrosis (CF) airways, mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) lead to dehydrated, thick mucus which promotes the establishment of persistent polymicrobial infections and drives chronic airways inflammation. This also predisposes the airways to further infections, a vicious, self-perpetuating cycle causing lung damage and progressive lung function decline. The airways are a poly-microbial environment, containing both aerobic and anaerobic bacterial species. Pseudomonas aeruginosa (P.aeruginosa) infections contribute to the excessive inflammatory response in CF, but the role of anaerobic Prevotella spp., frequently found in CF airways, is not known.Materials: We assessed innate immune signalling in CF airway epithelial cells in response to clinical strains of P.histicola, P.nigresens and P.aeruginosa. CFBE41o- cells were infected with P.aeruginosa (MOI 100, 2h) followed by infection with P.histicola or P.nigrescens (MOI 100, 2h). Cells were incubated under anaerobic conditions for the duration of the experiments.Results: Our study shows that P.histicola and P.nigresens can reduce the growth of P.aeruginosa and dampen the inflammatory response in airway epithelial cells. We specifically illustrate that the presence of Prevotella spp. reduces Toll-like-receptor (TLR)-4, MAPK, NF-kB(p65) signalling and cytokine release (Interleukin (IL)-6, IL-8) in mixed infections. Conclusion: Our work, for the first time, strongly indicates a relationship between P. aeruginosa and anaerobe Prevotella spp. The observed modified NF-kB and MAPK signalling provides some mechanisms of this interaction that could offer a novel therapeutic approach to combat chronic P.aeruginosa infection in people with CF.

Neutrophil elastase increases secretory leukocyte protease inhibitor transcript levels in airway epithelial cells

1993 ◽  
Vol 265 (3) ◽  
pp. L286-L292 ◽  
Author(s):  
J. M. Abbinante-Nissen ◽  
L. G. Simpson ◽  
G. D. Leikauf
Keyword(s):  
Epithelial Cells ◽  
Protease Inhibitor ◽  
Neutrophil Elastase ◽  
Airway Epithelial Cells ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Cathepsin G ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Necrosis Factor Alpha ◽  
Transcript Levels

Airway inflammation is often associated with the infiltration of activated neutrophils and subsequent protease release. Although aiding in the digestion and phagocytosis of foreign proteins and microorganisms, neutrophil proteases can indiscriminately damage healthy lung tissue. In the conducting airway, proteases, particularly neutrophil elastase, are counter-balanced by several antiproteases, including secretory leukocyte protease inhibitor (SLPI). SLPI can be produced locally by a number of cells including the airway epithelial cell. To examine the effects of neutrophil granule components on SLPI transcript levels, airway epithelial cells were treated (up to 96 h) with elastase, other proteases, or enzymes isolated from human sputum. We found that neutrophil elastase increased SLPI transcript levels in primary and transformed human airway epithelial cells in a time- and dose-dependent manner. Other neutrophil products, such as cathepsin G, myeloperoxidase, and lysozyme, had little or no effect on SLPI transcript levels. However, two nonneutrophil proteases, trypsin and pancreatic elastase, also increased SLPI transcript levels at higher doses than that required of neutrophil elastase. Two inflammatory cytokines, tumor necrosis factor-alpha and interleukin-8, produced little or no effect on SLPI transcript levels. This study demonstrates one way in which SLPI is regulated, via a protease that it inhibits, neutrophil elastase.

Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin

2004 ◽  
Vol 287 (1) ◽  
pp. L143-L152 ◽  
Author(s):  
Shawn J. Skerrett ◽  
H. Denny Liggitt ◽  
Adeline M. Hajjar ◽  
Robert K. Ernst ◽  
Samuel I. Miller ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Transgenic Mice ◽  
Lung Inflammation ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Respiratory Epithelial Cells ◽  
Distal Airway ◽  
Tnf Α ◽  
Respiratory Epithelial

To determine the role of respiratory epithelial cells in the inflammatory response to inhaled endotoxin, we selectively inhibited NF-κB activation in the respiratory epithelium using a mutant IκB-α construct that functioned as a dominant negative inhibitor of NF-κB translocation (dnIκB-α). We developed two lines of transgenic mice in which expression of dnIκB-α was targeted to the distal airway epithelium using the human surfactant apoprotein C promoter. Transgene expression was localized to the epithelium of the terminal bronchioles and alveoli. After inhalation of LPS, nuclear translocation of NF-κB was evident in bronchiolar epithelium of nontransgenic but not of transgenic mice. This defect was associated with impaired neutrophilic lung inflammation 4 h after LPS challenge and diminished levels of TNF-α, IL-1β, macrophage inflammatory protein-2, and KC in lung homogenates. Expression of TNF-α within bronchiolar epithelial cells and of VCAM-1 within peribronchiolar endothelial cells was reduced in transgenic animals. Thus targeted inhibition of NF-κB activation in distal airway epithelial cells impaired the inflammatory response to inhaled LPS. These data provide causal evidence that distal airway epithelial cells and the signals they transduce play a physiological role in lung inflammation in vivo.

Sign in / Sign up

Export Citation Format

Share Document