scholarly journals S100A9 in adult asthmatic patients: a biomarker for neutrophilic asthma

2021 ◽  
Author(s):  
Quang Luu Quoc ◽  
Youngwoo Choi ◽  
Tra Cao Thi Bich ◽  
Eun-Mi Yang ◽  
Yoo Seob Shin ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Macrophage Polarization ◽  
Serum Levels ◽  
Lavage Fluid ◽  
Airway Epithelial Cells ◽  
Neutrophil Activation ◽  
Neutrophil Extracellular Trap ◽  
Airway Epithelial ◽  
Asthmatic Patients ◽  
M1 Macrophage

AbstractThe biomarkers and therapeutic targets of neutrophilic asthma (NA) are poorly understood. Although S100 calcium-binding protein A9 (S100A9) has been shown to correlate with neutrophil activation, its role in asthma pathogenesis has not been clarified. This study investigated the mechanism by which S100A9 is involved in neutrophil activation, neutrophil extracellular trap (NET)-induced airway inflammation, and macrophage polarization in NA. The S100A9 levels (by ELISA) in sera/culture supernatant of peripheral blood neutrophils (PBNs) and M0 macrophages from asthmatic patients were measured and compared to those of healthy controls (HCs). The function of S100A9 was evaluated using airway epithelial cells (AECs) and PBNs/M0 macrophages from asthmatic patients, as well as a mouse asthma model. The serum levels of S100A9 were higher in NA patients than in non-NA patients, and there was a positive correlation between serum S100A9 levels and sputum neutrophil counts (r = 0.340, P = 0.005). Asthmatic patients with higher S100A9 levels had lower PC20 methacholine values and a higher prevalence of severe asthma (SA) (P < .050). PBNs/M0 macrophages from SA released more S100A9 than those from non-SA patients. PBNs from asthmatic patients induced S100A9 production by AECs, which further activated AECs via the extracellular signal-regulated kinase (ERK) pathway, stimulated NET formation, and induced M1 macrophage polarization. Higher S100A9 levels in sera, bronchoalveolar lavage fluid, and lung tissues were observed in the mouse model of NA but not in the other mouse models. These results suggest that S100A9 is a potential serum biomarker and therapeutic target for NA.

scholarly journals Bile Acids Repress Hypoxia-Inducible Factor 1 Signaling and Modulate the Airway Immune Response

2014 ◽  
Vol 82 (9) ◽  
pp. 3531-3541 ◽  
Author(s):  
Claire Legendre ◽  
F. Jerry Reen ◽  
David F. Woods ◽  
Marlies J. Mooij ◽  
Claire Adams ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Immune Response ◽  
Bile Acids ◽  
Respiratory Disease ◽  
Hypoxia Inducible Factor ◽  
Lavage Fluid ◽  
Airway Epithelial Cells ◽  
26S Proteasome ◽  
Specific Response ◽  
Airway Epithelial

ABSTRACTGastroesophageal reflux (GER) frequently occurs in patients with respiratory disease and is particularly prevalent in patients with cystic fibrosis. GER is a condition in which the duodenogastric contents of the stomach leak into the esophagus, in many cases resulting in aspiration into the respiratory tract. As such, the presence of GER-derived bile acids (BAs) has been confirmed in the bronchoalveolar lavage fluid and sputum of affected patients. We have recently shown that bile causes cystic fibrosis-associated bacterial pathogens to adopt a chronic lifestyle and may constitute a major host trigger underlying respiratory infection. The current study shows that BAs elicit a specific response in humans in which they repress hypoxia-inducible factor 1α (HIF-1α) protein, an emerging master regulator in response to infection and inflammation. HIF-1α repression was shown to occur through the 26S proteasome machinery via the prolyl hydroxylase domain (PHD) pathway. Further analysis of the downstream inflammatory response showed that HIF-1α repression by BAs can significantly modulate the immune response of airway epithelial cells, correlating with a decrease in interleukin-8 (IL-8) production, while IL-6 production was strongly increased. Importantly, the effects of BAs on cytokine production can also be more dominant than the bacterium-mediated effects. However, the effect of BAs on cytokine levels cannot be fully explained by their ability to repress HIF-1α, which is not surprising, given the complexity of the immune regulatory network. The suppression of HIF-1 signaling by bile acids may have a significant influence on the progression and outcome of respiratory disease, and the molecular mechanism underpinning this response warrants further investigation.

scholarly journals Dysfunctional ErbB2, an EGF receptor family member, hinders repair of airway epithelial cells from asthmatic patients

2019 ◽  
Vol 143 (6) ◽  
pp. 2075-2085.e10 ◽  
Author(s):  
Hideki Inoue ◽  
Takeshi Hattori ◽  
Xiuxia Zhou ◽  
Emily B. Etling ◽  
Brian D. Modena ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Family Member ◽  
Egf Receptor ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Asthmatic Patients ◽  
Egf Receptor Family ◽  
Receptor Family

Significance of thromboxane generation in ozone-induced airway hyperresponsiveness in dogs

1985 ◽  
Vol 59 (6) ◽  
pp. 1918-1923 ◽  
Author(s):  
H. Aizawa ◽  
K. F. Chung ◽  
G. D. Leikauf ◽  
I. Ueki ◽  
R. A. Bethel ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Thromboxane A2 ◽  
Lavage Fluid ◽  
Airway Epithelial Cells ◽  
Airway Responsiveness ◽  
Base Line ◽  
Airway Epithelial ◽  
Pulmonary Resistance ◽  
Fourfold Increase ◽  
Synthase Inhibitor

To determine whether thromboxane A2 may be involved in ozone (O3)-induced airway hyperresponsiveness, we studied the effect of a thromboxane synthase inhibitor (OKY-046, 100 micrograms X kg-1 X min-1 iv) in five dogs exposed to O3. Airway responsiveness was assessed by determining the provocative concentration of acetylcholine aerosol that increased total pulmonary resistance by 5 cmH2O X l-1 X s. O3 (3 ppm) increased airway responsiveness as demonstrated by a decrease in acetylcholine provocative concentration from 2.42 (geometric SEM = 1.64) to 0.14 mg/ml (geometric SEM = 1.30). OKY-046 significantly inhibited this effect without altering pre-O3 responsiveness or the O3-induced increase in neutrophils and airway epithelial cells in bronchoalveolar lavage fluid. To further examine the role of thromboxane A2, we studied the effect of a thromboxane A2 mimetic, U-46619, on airway responsiveness in five additional dogs. U-46619 in subthreshold doses (i.e., insufficient to increase base-line pulmonary resistance) caused a fourfold increase in airway responsiveness to acetylcholine. Subthreshold doses of histamine had no effect. These results suggest that thromboxane A2 may be an important mediator of O3-induced airway hyperresponsiveness.

scholarly journals Exercise Inhibits the Effects of Smoke-Induced COPD Involving Modulation of STAT3

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Maysa Alves Rodrigues Brandao-Rangel ◽  
Andre Luis Lacerda Bachi ◽  
Manoel Carneiro Oliveira-Junior ◽  
Asghar Abbasi ◽  
Adriano Silva-Renno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Collagen Fiber ◽  
Aerobic Training ◽  
Airway Remodeling ◽  
Pulmonary Inflammation ◽  
Serum Levels ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Male Mice ◽  
Lung Emphysema

Purpose. Evaluate the participation of STAT3 in the effects of aerobic exercise (AE) in a model of smoke-induced COPD. Methods. C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary inflammation, systemic inflammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results. AE inhibited smoke-induced accumulation of total cells (p<0.001), lymphocytes (p<0.001), and neutrophils (p<0.001) in BAL, as well as BAL levels of IL-1β (p<0.001), CXCL1 (p<0.001), IL-17 (p<0.001), and TNF-α (p<0.05), while increased the levels of IL-10 (p<0.001). AE also inhibited smoke-induced increases in total leukocytes (p<0.001), neutrophils (p<0.05), lymphocytes (p<0.001), and monocytes (p<0.01) in blood, as well as serum levels of IL-1β (p<0.01), CXCL1 (p<0.01), IL-17 (p<0.05), and TNF-α (p<0.01), while increased the levels of IL-10 (p<0.001). AE reduced smoke-induced emphysema (p<0.001) and collagen fiber accumulation in the airways (p<0.001). AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells (p<0.001), peribronchial leukocytes (p<0.001), and parenchymal leukocytes (p<0.001). Conclusions. AE reduces smoke-induced COPD phenotype involving STAT3.

scholarly journals Alterations in neutrophil extracellular traps is associated with the degree of decompensation of liver cirrhosis

2016 ◽  
Vol 10 (05) ◽  
pp. 512-517 ◽  
Author(s):  
Juan M Agraz-Cibrian ◽  
Jorge E Segura-Ortega ◽  
Vidal Delgado-Rizo ◽  
Mary Fafutis-Morris
Keyword(s):  
Liver Cirrhosis ◽  
Bacterial Infections ◽  
Causes Of Death ◽  
Serum Levels ◽  
Study Groups ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Activation ◽  
Neutrophil Extracellular Trap ◽  
Activation Markers ◽  
Extracellular Traps

Introduction: Liver cirrhosis (LC) constitutes one of the main 10 causes of death worldwide. LC has a characteristic asymptomatic compensated phase followed by a progressive decompensated phase, in which diverse complications are presented. LC patients are highly prone to bacterial infections. The neutrophils in these patients present defects in the production of oxygen radicals, which are essential for bacteria elimination as in the activation of neutrophil extracellular traps (NETs). The main objective of this work was to determine the NETs and neutrophil activation markers in LC patients. Methodology: Neutrophil purification was done with Ficoll Histopaque from a sample of the peripheral blood of patients with compensated and decompensated LC. Neutrophils were activated with Phorbol 12-myristate 13-acetate to evaluate the release of NETs by means of fluorescence microscopy and fluorometry, while expression of activation markers (CD69, CD80, perforin, and CAP-18) was evaluated by flow cytometry. Results: A significant decrease in the release capability of NETs was observed as the level of LC in the patient increased. When comparing serum levels in inflammatory cytokines among the different study groups, significant differences were observed. No significant differences were detected on neutrophil activation markers; nevertheless, there was a correlation between diminution of CD69 and CD80 expression in decompensated patients. Conclusions: We demonstrated that LC patients with neutrophil extracellular trap release deficiencies could have an increased rate of complications.

scholarly journals TRAIL signaling is proinflammatory and proviral in a murine model of rhinovirus 1B infection

2017 ◽  
Vol 312 (1) ◽  
pp. L89-L99 ◽  
Author(s):  
Jason L. Girkin ◽  
Luke M. Hatchwell ◽  
Adam M. Collison ◽  
Malcolm R. Starkey ◽  
Philip M. Hansbro ◽  
...  
Keyword(s):  
Apoptotic Cell ◽  
Lavage Fluid ◽  
Airway Epithelial Cells ◽  
Airway Hyperreactivity ◽  
Multiple Time ◽  
Airway Epithelial ◽  
Downstream Signaling ◽  
Multiple Time Points

the aim of this study is to elucidate the role of TRAIL during rhinovirus (RV) infection in vivo. Naïve wild-type and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-deficient ( Tnfsf10 −/−) BALB/c mice were infected intranasally with RV1B. In separate experiments, Tnfsf10 −/− mice were sensitized and challenged via the airway route with house dust mite (HDM) to induce allergic airways disease and then challenged with RVIB or UV-RVIB. Airway hyperreactivity (AHR) was invasively assessed as total airways resistance in response to increasing methacholine challenge and inflammation was assessed in bronchoalveolar lavage fluid at multiple time points postinfection. Chemokines were quantified by ELISA of whole lung lysates and viral load was determined by quantitative RT-PCR and tissue culture infective dose (TCID50). Human airway epithelial cells (BEAS2B) were infected with RV1B and stimulated with recombinant TRAIL or neutralizing anti-TRAIL antibodies and viral titer assessed by TCID50. HDM-challenged Tnfsf10 −/− mice were protected against RV-induced AHR and had suppressed cellular infiltration in the airways upon RV infection. Chemokine C-X-C-motif ligand 2 (CXCL2) production was suppressed in naïve Tnfsf10 −/− mice infected with RV1B, with less RV1B detected 24 h postinfection. This was associated with reduced apoptotic cell death and a reduction of interferon (IFN)-λ2/3 but not IFN-α or IFN-β. TRAIL stimulation increased, whereas anti-TRAIL antibodies reduced viral replication in RV1B-infected BEAS2B cells in vitro. In conclusion, TRAIL promotes RV-induced AHR, inflammation and RV1B replication, implicating this molecule and its downstream signaling pathways as a possible target for the amelioration of RV1B-induced allergic and nonallergic lung inflammation and AHR.

MTOR suppresses autophagy-mediated production of IL25 in allergic airway inflammation

Thorax ◽  
2020 ◽  
Vol 75 (12) ◽  
pp. 1047-1057
Author(s):  
Wen Li ◽  
Yinfang Wu ◽  
Yun Zhao ◽  
Zhouyang Li ◽  
Haixia Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Airway Epithelium ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Bronchial Epithelium ◽  
Airway Epithelial Cells ◽  
House Dust Mites ◽  
Airway Epithelial ◽  
Asthmatic Patients

IntroductionAirway epithelial cells are recognised as an essential controller for the initiation and perpetuation of asthmatic inflammation, yet the detailed mechanisms remain largely unknown. This study aims to investigate the roles and mechanisms of the mechanistic target of rapamycin (MTOR)–autophagy axis in airway epithelial injury in asthma.MethodsWe examined the MTOR–autophagy signalling in airway epithelium from asthmatic patients or allergic mice induced by ovalbumin or house dust mites, or in human bronchial epithelial (HBE) cells. Furthermore, mice with specific MTOR knockdown in airway epithelium and autophagy-related lc3b-/- mice were used for allergic models.ResultsMTOR activity was decreased, while autophagy was elevated, in airway epithelium from asthmatic patients or allergic mice, or in HBE cells treated with IL33 or IL13. These changes were associated with upstream tuberous sclerosis protein 2 signalling. Specific MTOR knockdown in mouse bronchial epithelium augmented, while LC3B deletion diminished allergen-induced airway inflammation and mucus hyperproduction. The worsened inflammation caused by MTOR deficiency was also ameliorated in lc3b-/- mice. Mechanistically, autophagy was induced later than the emergence of allergen-initiated inflammation, particularly IL33 expression. MTOR deficiency increased, while knocking out of LC3B abolished the production of IL25 and the eventual airway inflammation on allergen challenge. Blocking IL25 markedly attenuated the exacerbated airway inflammation in MTOR-deficiency mice.ConclusionCollectively, these results demonstrate that allergen-initiated inflammation suppresses MTOR and induces autophagy in airway epithelial cells, which results in the production of certain proallergic cytokines such as IL25, further promoting the type 2 response and eventually perpetuating airway inflammation in asthma.

Airway Epithelial Cells in Various Models of Bronchial Allergic Inflammation in Guinea Pigs

1992 ◽  
Vol 5 (3) ◽  
pp. 165-172
Author(s):  
J.P. Tarayre ◽  
M. Aliaga ◽  
M. Barbara ◽  
N. Malfetes ◽  
S. Vieu
Keyword(s):  
Epithelial Cells ◽  
Anaphylactic Reaction ◽  
Guinea Pigs ◽  
Allergic Inflammation ◽  
Lavage Fluid ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Freund’S Complete Adjuvant ◽  
Freund's Complete Adjuvant ◽  
Similar Intensity

The number of airway epithelial cells (AEC) in bronchus lumen after various types of anaphylactic shock of similar intensity was determined in guinea pigs. Aerosol-induced anaphylactic shocks were studied after four types of active sensitization: sensitization by IM injection of 30 mg/kg ovalbumin mixed with Freund's complete adjuvant; sensitization by IM injection of 30 mg/kg ovalbumin; sensitization by IP injection of 1 μg ovalbumin and 50 mg A1 (OH)3 by animal; sensitization by 2 exposures to 1%-ovalbumin aerosol at a 7-day interval. One, 3,6,24 and 48 h after the anaphylactic reaction the number of AEC in bronchoalveolar lavage fluid (BALF) was counted in comparison to guinea pigs sensitized but exposed to 0.9% NaCl aerosol. The number of AEC was significantly increased only 24–48 h after the shock in animals sensitized with ovalbumin in Freund's complete adjuvant. In animals passively sensitized by antiserum obtained with sensitization by ovalbumin in Freund's complete adjuvant and challenged by IV or aerosol administration of antigen, non rise in the number of AEC was obtained 24–48 h after the shock. The higher amount of AEC 24–48 h after the anaphylactic reaction in animals actively sensitized by ovalbumin in Freund's complete adjuvant could be related to the higher increase in the number of neutrophils and of mononuclears obtained in the BALF at these times in comparison to other types of active sensitization. The rise in the number of AEC only after the active reaction seems to show the part played by T-lymphocytes in the induction of this effect. The increase in the number of eosinophils in BALF and the appearance of the hyperreactivity cannot be related to the rise in the AEC in bronchus lumen.

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