Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung

Donovan, Chantal; Seow, Huei Jiunn; Bourke, Jane E.; Vlahos, Ross

doi:10.1042/cs20160093

Cited by 27 publications

(16 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Multiple sections can be obtained from a single lung, including human, 227 Rhesus Macaques, 228 marmosets 229 and mice. [230][231][232] SARS-CoV-2 replication in PCLS has not been established, but other viruses such as Adenovirus Type-7 can replicate in human, 233 swine IAV can replicate in pig 234 and respiratory syncytial virus can replicate in mouse PCLS. 235 The complexity of PCLS maintaining all cell types in their in vivo configuration is an advantage other culture techniques and the ability to directly compare between species is translational.…”

Section: Tissue Explantsmentioning

confidence: 99%

Animal and translational models of SARS-CoV-2 infection and COVID-19

et al. 2020

View full text Add to dashboard Cite

COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The major features of disease are described but clinical trials have been hampered by competing interests, small scale, lack of defined patient cohorts and defined readouts. What is needed now is head-to-head comparison of existing drugs, testing of safety including in the background of predisposing chronic diseases, and the development of new and targeted preventions and treatments. This is most efficiently achieved using representative animal models of primary infection including in the background of chronic disease with validation of findings in primary human cells and tissues. We explore and discuss the diverse animal, cell and tissue models that are being used and developed and collectively recapitulate many critical aspects of disease manifestation in humans to develop and test new preventions and treatments.

show abstract

Section: Tissue Explantsmentioning

confidence: 99%

Animal and translational models of SARS-CoV-2 infection and COVID-19

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In both acute and chronic CS‐exposure models, following IAV infection, increased pulmonary and systemic inflammation is observed. In some patients, increased viral proliferation or reduced clearance and decreased bronchodilator responses were noted . Exaggerated immune responses observed in CS exposure followed by infection was associated with increased expression of toll‐like receptor (TLR) 3 in the lungs of mice .…”

Section: Copd Exacerbationsmentioning

confidence: 99%

“…Patients with COPD have increased susceptibility to influenza A virus (IAV) infection and experience exaggerated inflammatory immune responses to infection. 3,41,59 In both acute and chronic CS-exposure models, following IAV infection, increased pulmonary and systemic inflammation is observed. In some patients, increased viral proliferation or reduced clearance and decreased bronchodilator responses were noted.…”

Section: Models Of Exacerbation: Viral Infectionsmentioning

confidence: 99%

“…In some patients, increased viral proliferation or reduced clearance and decreased bronchodilator responses were noted. 3,24,25,59 Exaggerated immune responses observed in CS exposure followed by infection was associated with increased expression of toll-like receptor (TLR) 3 in the lungs of mice. 60 Furthermore, CS-exposed TLR3 −/− mice were protected against the amplified inflammation and lung damage.…”

Section: Models Of Exacerbation: Viral Infectionsmentioning

confidence: 99%

See 1 more Smart Citation

Animal models of COPD: What do they tell us?

et al. 2016

Self Cite

View full text Add to dashboard Cite

COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanisms and identify biomarkers that may be therapeutic targets that would facilitate the development of improved standard of care. Here, we review the different established animal models of COPD and the various aspects of disease pathophysiology that have been successfully recapitulated in these models including chronic lung inflammation, airway remodelling, emphysema and impaired lung function. Furthermore, some of the mechanistic features, and thus biomarkers and therapeutic targets of COPD identified in animal models are outlined. Some of the existing therapies that suppress some disease symptoms that were identified in animal models and are progressing towards therapeutic development have been outlined. Further studies of representative animal models of human COPD have the strong potential to identify new and effective therapeutic approaches for COPD.

show abstract

“…PCLSs also benefit by preserving the native extracellular environment (Sanderson, 2011) and retaining nearly all of the resident cell types in the lung. These technical advantages have thus promoted widespread adoption of the PCLS in models of exposure assessment (Langer et al, 2012;Lauenstein et al, 2014;Uhl et al, 2015;Hess et al, 2016;Watson et al, 2016;Neuhaus et al, 2017), pharmacologic therapy (Switalla et al, 2010;van Rijt et al, 2015;Donovan et al, 2016;Kistemaker et al, 2017), and disease modeling, including chronic obstructive pulmonary disease (COPD) (Chronic Obstructive Lung Disease [COLD], 2017).…”

Section: Introductionmentioning

confidence: 99%

A High-Throughput System for Cyclic Stretching of Precision-Cut Lung Slices During Acute Cigarette Smoke Extract Exposure

et al. 2020

View full text Add to dashboard Cite

Rationale: Precision-cut lung slices (PCLSs) are a valuable tool in studying tissue responses to an acute exposure; however, cyclic stretching may be necessary to recapitulate physiologic, tidal breathing conditions. Objectives: To develop a multi-well stretcher and characterize the PCLS response following acute exposure to cigarette smoke extract (CSE). Methods: A 12-well stretching device was designed, built, and calibrated. PCLS were obtained from male Sprague-Dawley rats (N = 10) and assigned to one of three groups: 0% (unstretched), 5% peak-to-peak amplitude (low-stretch), and 5% peak-topeak amplitude superimposed on 10% static stretch (high-stretch). Lung slices were cyclically stretched for 12 h with or without CSE in the media. Levels of Interleukin-1β (IL-1β), matrix metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP1), and membrane type-MMP (MT1-MMP) were assessed via western blot from tissue homogenate. Results: The stretcher system produced nearly identical normal Lagrangian strains (E xx and E yy , p > 0.999) with negligible shear strain (E xy < 0.0005) and low intrawell variability 0.127 ± 0.073%. CSE dose response curve was well characterized by a four-parameter logistic model (R 2 = 0.893), yielding an IC 50 value of 0.018 cig/mL. Cyclic stretching for 12 h did not decrease PCLS viability. Two-way ANOVA detected a significant interaction between CSE and stretch pattern for IL-1β (p = 0.017), MMP-1, TIMP1, and MT1-MMP (p < 0.001). Conclusion: This platform is capable of high-throughput testing of an acute exposure under tightly-regulated, cyclic stretching conditions. We conclude that the acute mechano-inflammatory response to CSE exhibits complex, stretchdependence in the PCLS.

show abstract

Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung

Abstract: The present study has shown that the bronchodilator effectiveness of β-adrenoceptor agonists is diminished in CS and influenza A virus-induced lung disease and has identified the need for the development of novel bronchodilators for these diseases.

Cited by 27 publications

References 49 publications

Animal and translational models of SARS-CoV-2 infection and COVID-19

Animal and translational models of SARS-CoV-2 infection and COVID-19

Animal models of COPD: What do they tell us?

A High-Throughput System for Cyclic Stretching of Precision-Cut Lung Slices During Acute Cigarette Smoke Extract Exposure

Contact Info

Product

Resources

About