Jane Elizabeth Bourke

Jane Elizabeth Bourke
Monash University (Australia) · Department of Pharmacology

PhD

About

103
Publications
4,926
Reads
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1,275
Citations
Citations since 2016
46 Research Items
758 Citations
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
Additional affiliations
January 1997 - January 2014
University of Melbourne
Position
  • Professor (Associate)

Publications

Publications (103)
Article
Full-text available
Sulforaphane has been investigated in human pathologies and preclinical models of airway diseases. To provide further mechanistic insights, we explored L-sulforaphane (LSF) in the ovalbumin (OVA)-induced chronic allergic airways murine model, with key hallmarks of asthma. Histological analysis indicated that LSF prevented or reversed OVA-induced ep...
Article
Full-text available
SARS-CoV-2 infection causes a variety of physiological responses in the lung, and understanding how the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), and its proteolytic activator, transmembrane serine protease 2 (TMPRSS2), are affected in patients with underlying disease such as interstitial pneumonia will be important...
Article
Full-text available
Idiopathic pulmonary fibrosis is pathologically represented by usual interstitial pneumonia (UIP). Conventional bleomycin models used to study pathogenic mechanisms of pulmonary fibrosis display transient inflammation and fibrosis, so their relevance to UIP is limited. We developed a novel chronic induced-UIP (iUIP) model, inducing fibrosis in D1CC...
Article
Airway smooth muscle is the primary effector regulating bronchomotor tone, and plays a major role in lung diseases, particularly asthma. Contraction was previously considered its sole function; the classical sliding filament theory has now advanced to models that allow the muscle to adapt and function under oscillatory loads. A new paradigm has eme...
Preprint
Full-text available
Sulforaphane has been investigated in human pathologies and preclinical models of airway diseases. To provide further mechanistic insights, we explored L-sulforaphane (LSF) in the ovalbumin (OVA)-induced chronic allergic airways murine model, with key hallmarks of asthma. Histological analysis indicated that LSF prevented or reversed OVA-induced ep...
Article
Asthma (chronic allergic airways disease, AAD) is characterized by airway inflammation (AI), airway remodeling (AWR) and airway hyperresponsiveness (AHR). Current treatments for AAD mainly focus on targeting AI and its contribution AHR, with the use of corticosteroids. However, there are no therapies for the direct treatment of AWR, which can contr...
Preprint
Full-text available
Idiopathic pulmonary fibrosis (IPF) is pathologically classified by usual interstitial pneumonia (UIP). Conventional bleomycin models used to study pathogenic mechanisms of pulmonary fibrosis display transient inflammation and fibrosis so their relevance to UIP is limited. We developed a novel chronic i nduced-UIP (iUIP) model, inducing fibrosis in...
Article
The CaSR is a class C G protein-coupled receptor (GPCR) that acts as a multimodal chemosensor to maintain diverse homeostatic functions. The CaSR is a clinical therapeutic target in hyperparathyroidism and has emerged as a putative target in several other diseases. These include hyper- and hypocalcaemia caused either by mutations in the CASR gene o...
Article
Full-text available
Background The receptor for advanced glycation end products (RAGE) and toll‐like receptor 4 (TLR4) are implicated in COPD. Although these receptors share common ligands and signaling pathways, it is not known whether they act in concert to drive pathological processes in COPD. We examined the impact of RAGE and/or TLR4 gene deficiency in a mouse mo...
Article
Full-text available
Pulmonary hypertension secondary to bronchopulmonary dysplasia (BPD-PH) represents a major complication of BPD in extremely preterm infants for which there are currently no safe and effective interventions. The abundance of interleukin-1 (IL-1) is strongly correlated with the severity and long-term outcome of BPD infants and we have previously show...
Chapter
Airway smooth muscle (ASM) extends from the trachea throughout the bronchial tree to the terminal bronchioles. In utero, spontaneous phasic contraction of fetal ASM is critical for normal lung development by regulating intraluminal fluid movement, ASM differentiation, and release of key growth factors. In contrast, phasic contraction appears to be...
Article
Full-text available
The anti-inflammatory, pro-resolving annexin-A1 protein acts as an endogenous brake against exaggerated cardiac necrosis, inflammation, and fibrosis following myocardial infarction (MI) in vivo. Little is known, however, regarding the cardioprotective actions of the N-terminal-derived peptide of annexin A1, Ac2-26, particularly beyond its anti-necr...
Article
Background Asthma and allergic diseases are heterogeneous. Measurement of biomarkers in exhaled breath condensate (EBC) may help to discriminate between different phenotypes and may assist with clinical prognostication. Objectives We aimed to assess associations between total nitric oxide products (NOx) in EBC and different allergic phenotypes and...
Article
The most common therapies for asthma and other chronic lung diseases are anti-inflammatory agents and bronchodilators. While these drugs oppose disease symptoms, they do not reverse established structural changes in the airways and their therapeutic efficacy is reduced with increasing disease severity. The peptide hormone, relaxin, is a Relaxin Fam...
Article
Asthma is a chronic inflammatory disease of the airways. It is characterised by allergic airway inflammation, remodelling and hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation of extracellular matrix (ECM) proteins, such as collagens. Fibul...
Article
Full-text available
Effective treatment for managing myocardial infarction (MI) remains an urgent, unmet clinical need. Formyl peptide receptors (FPR) regulate inflammation, a major contributing mechanism to cardiac injury following MI. Here we demonstrate that FPR1/FPR2-biased agonism may represent a novel therapeutic strategy for the treatment of MI. The small-molec...
Data
Supplementary Tables and Supplementary Figures.
Article
Full-text available
Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy...
Article
Objective: Glyceryl trinitrate (GTN) is used to treat angina and lower blood pressure. The enzyme mitochondrial aldehyde dehydrogenase-2 (ALDH2) can activate GTN. The polymorphism (Gly504Lys) in the gene encoding ALDH2 is associated with significantly reduced enzyme activity and potentially diminished responses to GTN. Design and method: Systoli...
Article
Full-text available
Bronchopulmonary dysplasia (BPD) is a chronic disease of extreme prematurity that has serious long-term consequences including increased asthma risk. We earlier identified IL-1 receptor antagonist (IL-1Ra) as a potent inhibitor of murine BPD induced by combining perinatal inflammation (intra-peritoneal lipopolysaccharide to pregnant dams) and expos...
Article
Full-text available
Background Asthma affects 300 million people worldwide. In asthma, the major cause of morbidity and mortality is acute airway narrowing, due to airway smooth muscle (ASM) hypercontraction, associated with airway remodelling. However, little is known about the transcriptional differences between healthy and asthmatic ASM cells. Objectives To investi...
Article
Full-text available
β2-adrenoceptor agonists are the mainstay therapy for patients with asthma but their effectiveness in cigarette smoke (CS)-induced lung disease such as chronic obstructive pulmonary disease (COPD) is limited. In addition, bronchodilator efficacy of β2-adrenoceptor agonists is decreased during acute exacerbations of COPD (AECOPD), caused by respirat...
Article
Full-text available
There is emerging epidemiological data to suggest that upper respiratory tract bacterial colonisation in infancy may increase the risk of developing respiratory dysfunction later in life, and respiratory viruses are known to precipitate persistent colonisation. This study utilized a neonatal mouse model of Streptococcus pneumonia (SP) and influenza...
Article
Full-text available
Oxidative stress has a recognised role in the pathophysiology of asthma. Recently, interest has increased in the assessment of pH and airway oxidative stress markers. Collection of exhaled breath condensate (EBC) and quantification of biomarkers in breath samples can potentially indicate lung disease activity and help in the study of airway inflamm...
Article
Lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are highly prevalent worldwide. One of the major factors that limits the efficacy of current medication in these patients are viral infections, leading to exacerbations of symptoms and decreased quality of life. Current pharmacological strategies targeting virus-induced...
Article
Full-text available
Rosiglitazone (RGZ), a Peroxisome Proliferator Activated Receptor γ (PPARγ) ligand, is a novel dilator of small airways in mouse precision cut lung slices (PCLS). In this study, relaxation to RGZ and β-adrenoceptor agonists were compared in trachea from naïve mice and guinea pigs, and trachea and PCLS from a mouse model of chronic allergic airways...
Article
Introduction: Bronchopulmonary dysplasia (BPD) is a chronic disease associated with pre-term birth, with serious consequences including increased asthma risk. We hypothesised that reduced alveolar development in BPD could contribute to altered airway reactivity in the peripheral lung. Aim: To characterise alveolar changes and small airway contracti...
Article
Full-text available
Introduction: Influenza infections commonly cause acute exacerbations of chronic obstructive pulmonary disease (AECOPD). AECOPD trigger an accelerated decline in lung function, leading to hospitalisation and in some cases death. The majority of COPD patients have small airway obstruction, which contributes to dyspnea and decreased efficacy of curre...
Conference Paper
Introduction: The organ-protective drug, serelaxin (RLN), relaxes uterine and vascular smooth muscle and mediates anti-fibrotic actions through its cognate receptor, RXFP1, and nitric oxide. Its potential to oppose airway contraction has yet to be characterized. Aim: To compare the effects of RLN with rosiglitazone (RGZ, a PPARγ agonist) and isopr...
Article
Full-text available
The bacterial endotoxin, lipopolysaccharide (LPS) has been associated with occupational airway diseases with asthma-like symptoms and in acute exacerbations of COPD. The direct and indirect effects of LPS on small airway reactivity have not been fully elucidated. We tested the hypothesis that both in vitro and in vivo LPS treatment would increase c...
Article
Small airways are a major site of airflow limitation in chronic obstructive pulmonary disease (COPD). Despite the detrimental effects of long-term smoking in COPD, the effects of acute cigarette smoke exposure on small airway reactivity have not been fully elucidated. Balb/C mice were exposed to room air (sham) or cigarette smoke for 4 days to caus...
Article
Myocardial infarction (MI) is the major cause of heart failure and death in the Western world. Annexin-A1 is an endogenous, glucocorticoid-regulated anti-inflammatory protein. We have previously shown that this protein plays an important protective role in preserving left ventricular (LV) viability and function in vitro, actions that are reproduced...
Article
BACKGROUND: Asthma is a widespread chronic health problem exacerbated by common viral and bacterial infections. Further research is required to understand how infection worsens asthma control in order to advance therapeutic options in the future. Recent research has revealed that β2 -adrenergic receptor (β2 -AR) agonists lose bronchodilatory effic...
Article
Background Asthma is a widespread chronic health problem exacerbated by common viral and bacterial infections. Further research is required to understand how infection worsens asthma control in order to advance therapeutic options in the future. Recent research has revealed that β2-adrenergic receptor (β2-AR) agonists lose bronchodilatory efficacy...
Article
Full-text available
Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characterise responses to the recently identified novel bronchodilators rosiglitazone (RGZ) and chloroquine (CQ) under conditions where beta-adrenoceptor agonist efficacy was limited or impai...
Article
Full-text available
There is a pressing need to identify novel agents that elicit small airway relaxation when β2-adrenoceptor agonists become ineffective in difficult-to-treat asthma. Because chronic treatment with the synthetic peroxisome proliferator activated receptor γ (PPARγ) agonist rosiglitazone (RGZ) inhibits airway hyperresponsiveness in mouse models of alle...
Article
Full-text available
The relative contributions of large and small airways to hyperresponsiveness in asthma have yet to be fully assessed. This study used a mouse model of chronic allergic airways disease to induce inflammation and remodelling and determine whether in vivo hyperresponsiveness to methacholine is consistent with in vitro reactivity of trachea and small a...