Do eosinophils contribute to oxidative stress in mild asthma?

Groot, Linsey E. S. de; Piñeros, Yanaika S. Sabogal; Bal, Suzanne M.; Pol, Marianne A. van de; Hamann, Jörg; Sterk, Peter J.; Kulik, Wim; Lutter, René

doi:10.1111/cea.13389

Cited by 27 publications

(17 citation statements)

References 10 publications

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“…It has been previously shown that experimental rhinovirus infection induces oxidative stress in mild asthmatics, particularly in those with high eosinophil counts. Depletion of eosinophils resulted in reduced oxidative stress after rhinovirus infection in this group, demonstrating the role of oxidative stress at exacerbations (39). In this study, both live rhinovirus infection and stimulation with the synthetic viral replication intermediate poly(I:C) induces antioxidant expression in bronchial epithelial cells obtained from diseased individuals.…”

Section: Discussionmentioning

confidence: 76%

Oxidative Stress Attenuates TLR3 Responsiveness and Impairs Anti-viral Mechanisms in Bronchial Epithelial Cells From COPD and Asthma Patients

et al. 2019

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COPD and asthma exacerbations are commonly triggered by rhinovirus infection. Potentially promoting exacerbations, impaired anti-viral signaling and attenuated viral clearance have been observed in diseased bronchial epithelium. Oxidative stress is a feature of inflammation in asthma and COPD and is prominent during exacerbations. It is not known whether oxidative stress affects the anti-viral signaling capacity. Bronchial epithelial cells from asthmatic and COPD donors were infected with rhinovirus or treated with the oxidative stressor H2O2 followed by exposure to the synthetic viral replication intermediate poly(I:C). Poly(I:C) was used to ascertain a constant infection-like burden. Gene and protein levels of antioxidants as well as anti-viral responses were measured 3 and 24 h post poly(I:C) exposure. Rhinovirus infection and poly(I:C) stimulation induced protein levels of the antioxidants SOD1 and SOD2. In asthmatic bronchial epithelial cells pre-treatment with H2O2 dose-dependently decreased the antioxidant response to poly(I:C), suggesting exaggerated oxidative stress. Further, poly(I:C)-induced IFNβ gene expression was reduced after pre-treatment with H2O2. This epithelial effect was associated with a reduced expression of the pattern recognition receptors RIG-I, MDA5 and TLR3 both on gene and protein level. Pre-treatment with H2O2 did not alter antioxidant responses in COPD bronchial epithelial cells and, more modestly than in asthma, reduced poly(I:C)-induced IFNβ gene expression. Knockdown of TLR3 but not RIG-I/MDA5 abrogated impairment of poly(I:C)-induced IFNβ gene expression by H2O2. We developed a method by which we could demonstrate that oxidative stress impairs anti-viral signaling in bronchial epithelial cells from asthmatic and COPD patients, most pronounced in asthma. The impairment apparently reflects reduced responsiveness of TLR3. These present findings shed light on molecular mechanisms potentially causing reduced interferon responses to rhinovirus infection at exacerbations in asthma and COPD. Together, our findings suggest a possible self-perpetuating vicious cycle underlying recurrent exacerbations, leading to an impaired anti-viral response, which in turn leads to viral-induced exacerbations, causing more airway inflammation.

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Section: Discussionmentioning

confidence: 76%

Oxidative Stress Attenuates TLR3 Responsiveness and Impairs Anti-viral Mechanisms in Bronchial Epithelial Cells From COPD and Asthma Patients

et al. 2019

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“…The published data indicate that the Eo activation results in oxidative stress [21], whether the oxidative species are increased inside Eos in response to exposing specific antigens remain to be elucidated. Prompted by the fact of exposing to specific antigens can activate sensitized Eos [9], we developed an asthma mouse model; the mice were challenged with nasal instillation containing the specific antigen, OVA, together with or without FGN in the course of sensitization.…”

Section: Resultsmentioning

confidence: 99%

Flagellin Alleviates Airway Allergic Response by Stabilizing Eosinophils through Modulating Oxidative Stress

Luo

et al. 2021

J Innate Immun

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Eosinophil (Eo) degranulation plays a central role in the initiations of allergic attacks. Flagellin (FGN), the major component of bacterial flagella, has immune regulatory functions. This study aims to investigate the role of FGN in alleviating the allergic reaction by stabilizing Eos. A toll-like receptor 5-knockout mouse strain was employed to test the role of FGN in stabilizing Eos. An airway allergy mouse model was developed to test the administration of FGN in alleviating the airway allergy by stabilizing Eos. The results showed that FGN was required in stabilizing Eos in the airway tissues. FGN prevented specific antigen-induced Eo activation. Oxidative stress was associated with the antigen-induced Eo activation that could be counteracted by the presence of FGN. The FGN levels were lower and chymase levels were higher in the airway tissues of mice with allergic inflammation. Negative correlation was detected between the data of FGN and chymase in the lung tissues. Chymase physically contacted FGN to speed up its degradation. The administration of FGN alleviated experimental allergic inflammation in the mouse airways by stabilized Eos in the lung tissues. In conclusion, FGN contributes to Eo stabilization. The administration of FGN alleviates the experimental airway allergy. The data suggest that FGN can be a candidate to be employed in the treatment of allergic disorders.

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“…Eosinophils contribute to oxidative stress in mild asthma and targeting oxidative stress could be considered as a treatment option during asthma exacerbations [ 298 ]. Preclinical data from Silveira et al demonstrated that the ROS inhibitors N-acetylcysteine or diphenyleneiodonium reduced eosinophil extracellular trap formation by eosinophils and ameliorated airway inflammation [ 287 ].…”

Section: Non-enzymatic Lipid Peroxidationmentioning

confidence: 99%

Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids

Knuplez

Sturm

Marsche

2021

IJMS

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Eosinophils are important effector cells involved in allergic inflammation. When stimulated, eosinophils release a variety of mediators initiating, propagating, and maintaining local inflammation. Both, the activity and concentration of secreted and cytosolic phospholipases (PLAs) are increased in allergic inflammation, promoting the cleavage of phospholipids and thus the production of reactive lipid mediators. Eosinophils express high levels of secreted phospholipase A2 compared to other leukocytes, indicating their direct involvement in the production of lipid mediators during allergic inflammation. On the other side, eosinophils have also been recognized as crucial mediators with regulatory and homeostatic roles in local immunity and repair. Thus, targeting the complex network of lipid mediators offer a unique opportunity to target the over-activation and ‘pro-inflammatory’ phenotype of eosinophils without compromising the survival and functions of tissue-resident and homeostatic eosinophils. Here we provide a comprehensive overview of the critical role of phospholipase-derived lipid mediators in modulating eosinophil activity in health and disease. We focus on lysophospholipids, polyunsaturated fatty acids, and eicosanoids with exciting new perspectives for future drug development.

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Do eosinophils contribute to oxidative stress in mild asthma?

Cited by 27 publications

References 10 publications

Oxidative Stress Attenuates TLR3 Responsiveness and Impairs Anti-viral Mechanisms in Bronchial Epithelial Cells From COPD and Asthma Patients

Oxidative Stress Attenuates TLR3 Responsiveness and Impairs Anti-viral Mechanisms in Bronchial Epithelial Cells From COPD and Asthma Patients

Flagellin Alleviates Airway Allergic Response by Stabilizing Eosinophils through Modulating Oxidative Stress

Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids

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