Airway Hyperresponsiveness Is Severe and Persistent in an Equine Model of Neutrophilic Asthma

Hunter, Courtney; Bowser, J.E.; Wills, Robert W.; Byars, Priscilla; Moore, Jessica W; Wilson, Rachel M.; Byrne, R.J.; Swiderski, Cyprianna E.

doi:10.1165/rcmb.2019-0049le

Cited by 4 publications

(8 citation statements)

References 14 publications

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“…Then, we found that CAD improved general conditions in asthma model mice, as evidenced by decreasing the number of sneezing and catching nose, respiratory rate, as well as increased tidal volume. Airway hyperresponsiveness, as one of the main characteristics of chronic asthma, is caused by airway inflammation [ 26 , 27 ]. Hence, we explored the changes in airway activity immediately after the RSV-infected asthma mice model was treated with CAD, and the results have shown that CAD effectively attenuated the airway hyperresponsiveness under stimulation with different concentrations of acetylcholine.…”

Section: Discussionmentioning

confidence: 99%

Conciliatory Anti-Allergic Decoction Attenuates Pyroptosis in RSV-Infected Asthmatic Mice and Lipopolysaccharide (LPS)-Induced 16HBE Cells by Inhibiting TLR3/NLRP3/NF-κB/IRF3 Signaling Pathway

Chen

Zhou

Wang

et al. 2022

Journal of Immunology Research

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Respiratory syncytial virus (RSV) infection can deteriorate asthma by inducing persistent airway inflammation. Increasing evidence elucidated that pyroptosis plays a pivotal role in asthma. Conciliatory anti-allergic decoction (CAD) exhibits an anti-inflammatory effect in ovalbumin (OVA)-induced asthma; however, the effects and mechanisms of CAD in RSV-infected asthmatic mice have not yet been elucidated. The RSV-infected asthmatic mice model and lipopolysaccharide (LPS)-induced 16HBE cell pyroptosis model were established, respectively. Pulmonary function, ELISA, and histopathologic analysis were performed to assess the airway inflammation and remodeling in mice with CAD treatment. Furthermore, ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) was conducted to identify the chemical compounds of high-dose CAD (30 g/kg). Cell viability and apoptosis of 16HBE cells were assessed by CCK-8 and flow cytometry assays, respectively. Finally, the expression levels of apoptosis-, pyroptosis-, and TLR3/NLRP3/NF-κB/IRF3 signaling-related genes were measured with qRT-PCR or western blotting, respectively. Pulmonary function tests showed that CAD significantly ameliorated respiratory dysfunction, airway hyperresponsiveness, inflammation cell recruitment in BALF, pulmonary inflammation, collagen deposition, and cell death in lung tissues. CAD significantly decreased the content of TNF-α, IL-13, IL-4, IL-1β and IL-5 in the bronchoalveolar lavage fluid (BALF), IL-17, IL-6, and OVA-specific IgE in serum and increased serum IFN-γ in asthma mice. The results of UPLC-Q-TOF/MS showed that high-dose CAD had 88 kinds of chemical components. In vitro, CAD-contained serum significantly suppressed LPS-induced 16HBE cell apoptosis. Additionally, CAD and CAD-contained serum attenuated the up-regulated expressions of Bax, Cleaved caspase-3, NLRP3, ASC, Cleaved caspase-1, GSDMD-N, IL-18, IL-1β, TLR3, p-P65, p-IκBα, and IRF3 but increased Bcl-1 and GSDMD levels in the asthma mice and LPS-induced 16HBE cells, respectively. These results illustrated that CAD may have a potential role in improving airway inflammation and pyroptosis through inhibition of the TLR3/NLRP3/NF-κB/IRF3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Conciliatory Anti-Allergic Decoction Attenuates Pyroptosis in RSV-Infected Asthmatic Mice and Lipopolysaccharide (LPS)-Induced 16HBE Cells by Inhibiting TLR3/NLRP3/NF-κB/IRF3 Signaling Pathway

Chen

Zhou

Wang

et al. 2022

Journal of Immunology Research

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“…ASM plays a pivotal role in the pathophysiology of asthma and COPD as it contributes to the bronchoconstriction, airway hyperresponsiveness (AHR), airway remodelling, and inflammation that characterise these diseases, now recognised as two separate disorders characterised by different aetiology, symptoms, inflammatory profile, airway narrowing, response to therapy and time course (Cukic et al, 2012;Doeing & Solway, 2013). Although it is extensively recognised that ASM is a crucial target in the treatment of both of these chronic obstructive respiratory disorders, to date the pathophysiology of human airway narrowing that characterises asthma and COPD remains only partially understood (Bates, 2016;Hulsmann & de Jongste, 1993;Mauad & Dolhnikoff, 2008).…”

Section: Animal Versus Human Isolated Airwaysmentioning

confidence: 99%

“…Therefore, in order to gain more insight into the underlying processes of asthma and COPD, many animal models have been developed. However, significant differences between commonly used experimental animal species (particularly mice) and humans exist (Hulsmann & de Jongste, 1993).…”

Section: Animal Versus Human Isolated Airwaysmentioning

confidence: 99%

“…Overall, considering the difficulties associated with studying small experimental animals, the poor predictive value of murine ASM contractile regulation with respect to human airways, and the costs and management of models in large animals, to date there is no ideal preclinical model in experimental animals for understanding chronic obstructive respiratory disorders (Aun et al, 2017;Brusselle et al, 2006;Canning, 2006;Kips et al, 2003;Van der Velden & Snibson, 2011). There remains therefore a need to, where possible, investigate human tissues to better understand human diseases and the use of isolated human airways represents a valid approach to investigate drugs for the treatment of chronic obstructive respiratory disorders (Black et al, 2012;Blume & Davies, 2013;Calzetta, Matera, et al, 2019a;Hulsmann & de Jongste, 1993;Persson, 2002;Roux et al, 1999;Selo et al, 2021). Effectively, several bench-to-bedside studies have demonstrated that results obtained from well-performed experiments on isolated human airways can be translated into the clinical setting (Calzetta, Aiello, Frizzelli, Bertorelli, & Chetta, 2022a;Calzetta, Matera, et al, 2019a;Calzetta, Pistocchini, et al, 2019b;Cazzola, Calzetta, Ora, et al, 2015a;Cazzola, Calzetta, Segreti, et al, 2015b;Rogliani et al, 2015;Rogliani, Ora, Girolami, et al, 2021a).…”

Section: Animal Versus Human Isolated Airwaysmentioning

confidence: 99%

“…In the laboratory, the airways are cut into rings with surgical scissors to produce medium isolated bronchial rings (thickness 1-2 mm) that are mounted into isolated, multi-channel organ bath systems. This is the most effective technique to prepare medium isolated bronchi to be studied in vitro in organ bath systems because it needs usually less than 100 mg of tissue, the tissue damage is reduced, and the ASM bundle is preserved (Calzetta, Aiello, et al, 2021a;Calzetta, Ora, et al, 2017a;Hulsmann & de Jongste, 1993;Ritondo et al, 2021).…”

Section: Tissue Collection Preparation and Equipmentmentioning

confidence: 99%

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Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

Calzetta,

Page,

Matera

et al. 2023

British J Pharmacology

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Isolated airway smooth muscle has been extensively investigated since 1840 to understand the pharmacology of airway diseases. There has been often poor predictability from murine experiments to drugs evaluated in patients with asthma or chronic obstructive pulmonary disease (COPD). However, the use of isolated human airways represents a sensible strategy to optimise the development of innovative molecules for the treatment of respiratory diseases. This review aims to provide updated evidence on the current uses of isolated human airways in validated in vitro methods to investigate drugs in development for the treatment of chronic obstructive respiratory disorders. This review also provides historical notes on the pioneering pharmacological research on isolated human airway tissues, the key differences between human and animal airways, as well as the pivotal differences between human medium bronchi and small airways. Experiments carried out with isolated human bronchial tissues in vitro and ex vivo replicate many of the main anatomical, pathophysiological, mechanical and immunological characteristics of patients with asthma or COPD. In vitro models of asthma and COPD using isolated human airways can provide information that is directly translatable into humans with obstructive lung diseases. Regardless of the technique used to investigate drugs for the treatment of chronic obstructive respiratory disorders (i.e. isolated organ bath systems, videomicroscopy, wire myography), the most limiting factors to produce high‐quality and repeatable data remain closely tied to the manual skills of the researcher conducting experiments and the availability of suitable tissue.

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LXA4 inhibits TGF-β1-induced airway smooth muscle cells proliferation and migration by suppressing the Smad/YAP pathway

Zhao

Zhang

Wang

et al. 2023

International Immunopharmacology

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Airway Hyperresponsiveness Is Severe and Persistent in an Equine Model of Neutrophilic Asthma

Cited by 4 publications

References 14 publications

Conciliatory Anti-Allergic Decoction Attenuates Pyroptosis in RSV-Infected Asthmatic Mice and Lipopolysaccharide (LPS)-Induced 16HBE Cells by Inhibiting TLR3/NLRP3/NF-κB/IRF3 Signaling Pathway

Conciliatory Anti-Allergic Decoction Attenuates Pyroptosis in RSV-Infected Asthmatic Mice and Lipopolysaccharide (LPS)-Induced 16HBE Cells by Inhibiting TLR3/NLRP3/NF-κB/IRF3 Signaling Pathway

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

LXA4 inhibits TGF-β1-induced airway smooth muscle cells proliferation and migration by suppressing the Smad/YAP pathway

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