A5060211723- Chronic Obstructive Pulmonary Disease (COPD) Research
- Asthma and respiratory diseases
- Immune Response and Inflammation
- Respiratory Support and Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pediatric health and respiratory diseases
- Influenza Virus Research Studies
- Neonatal Respiratory Health Research
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- IL-33, ST2, and ILC Pathways
- Pulmonary Hypertension Research and Treatments
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Nitric Oxide and Endothelin Effects
- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Inflammasome and immune disorders
- Inhalation and Respiratory Drug Delivery
- Psoriasis: Treatment and Pathogenesis
- Redox biology and oxidative stress
- Eicosanoids and Hypertension Pharmacology
- Inflammation biomarkers and pathways
- Protease and Inhibitor Mechanisms
- Exercise and Physiological Responses
- Phagocytosis and Immune Regulation
RMIT University
2016-2025
MIT University
2015-2023
The University of Melbourne
2010-2019
Berkeley Public Health Division
2018
University of California, Berkeley
2018
Health Innovations (United States)
2015-2016
Monash University
2000-2014
The Royal Melbourne Hospital
2004-2006
UNSW Sydney
2005-2006
The University of Queensland
2005
Influenza A virus pandemics and emerging anti-viral resistance highlight the urgent need for novel generic pharmacological strategies that reduce both viral replication lung inflammation. We investigated whether primary enzymatic source of inflammatory cell ROS (reactive oxygen species), Nox2-containing NADPH oxidase, is a target against inflammation caused by influenza viruses. Male WT (C57BL/6) Nox2(-/y) mice were infected intranasally with low pathogenicity (X-31, H3N2) or higher (PR8,...
Rationale: Much of the total disease burden and cost chronic obstructive pulmonary (COPD) is associated with acute exacerbations COPD (AECOPD). Serum amyloid A (SAA) a novel candidate exacerbation biomarker identified by proteomic screening. Objectives: To assess SAA as AECOPD.Methods: Biomarkers were assessed (1) cross-sectionally (stable vs. AECOPD; 62 individuals) (2) longitudinally repeated measures (baseline AECOPD convalescence; 78 episodes in 37 individuals). Event severity was graded...
Cigarette smoke exposure is a major determinant of adverse lung health, but the molecular processes underlying its effects on inflammation and immunity remain poorly understood. Therefore, we sought to understand whether inflammatory host defense determinants are affected during subchronic cigarette exposure. Dose-response time course studies lungs from Balb/c mice exposed generated 3, 6, 9 cigarettes/day for 4 days showed macrophage- S100A8-positive neutrophil-rich in tissue bronchoalveolar...
Chronic obstructive pulmonary disease (COPD) will soon be the third most common cause of death globally. Despite smoking cessation, neutrophilic mucosal inflammation persistently damages airways and fails to protect from recurrent infections. This maladaptive excess is also refractory glucocorticosteroids (GC). Here, we identify serum amyloid A (SAA) as a candidate mediator GC in COPD. Extrahepatic SAA was detected locally COPD bronchoalveolar lavage fluid, which correlated with IL-8...
Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease that unresponsive to current therapies and characterized by excessive collagen deposition subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)‐6, are elevated in IPF, the molecular mechanisms underlie this incompletely understood, although development of believed depend on canonical transforming growth factor (TGF)‐β signalling. We examined bleomycin‐induced inflammation mice carrying mutation shared...
Cigarette smoke has both pro-inflammatory and immunosuppressive effects. Both active passive cigarette exposure are linked to an increased incidence severity of respiratory virus infections, but underlying mechanisms not well defined. We hypothesized, based on prior gene expression profiling studies, that upregulation mediators by short term would be protective against a subsequent influenza infection. BALB/c mice were subjected whole body with 9 cigarettes/day for 4 days. Mice then infected...
The imminent threat of viral epidemics and pandemics dictates a need for therapeutic approaches that target pathology irrespective the infecting strain. Reactive oxygen species are ancient processes protect plants, fungi animals against invading pathogens including bacteria. However, in mammals reactive production paradoxically promotes virus pathogenicity by mechanisms not yet defined. Here we identify primary enzymatic source species, NOX2 oxidase, is activated single stranded RNA DNA...
Although great progress has been made in delineating lung dendritic cell and lymphocyte subpopulations, similar advances macrophages (MΦs) have hampered by their intrinsic autofluorescence, plasticity, the complexities of monocyte-MΦ compartmentalization. Using spectral scanning, we define alveolar MΦ autofluorescence characteristics, which allowed us to develop an alternative flow cytometry method. this methodology, show that mouse MΦs form distinct subpopulations during acute inflammation...
Aims: Reactive oxygen species (ROS) are highly reactive molecules generated in different subcellular sites or compartments, including endosomes via the NOX2-containing nicotinamide adenine dinucleotide phosphate oxidase during an immune response and mitochondria cellular respiration. However, while endosomal NOX2 promotes innate inflammation to influenza A virus (IAV) infection, role of mitochondrial ROS (mtROS) has not been comprehensively investigated context viral infections vivo....
The lung innate immune response to lipopolysaccharide (LPS) coordinates cellular inflammation, mediator, and protease release essential for host defense but deleterious in asthma, chronic obstructive pulmonary disease, cystic fibrosis. <i>In vitro</i>, LPS signals the transcription factors NFκB via TLR4, MyD88, IL-1R-associated kinase (IRAK), AP-1 by mitogen-activated protein (MAP) kinases, an alternate route <i>IRAK</i>-deficient mice, <i>in vivo</i>lung signaling pathway(s) are not...
There is recent interest in the role of monocyte/macrophage subpopulations pathology. How hemopoietic growth factors, macrophage‐colony stimulating factor (M‐CSF or CSF‐1) and granulocyte macrophage (GM)‐CSF, regulate their vivo development function unclear. A comparison made here on effect CSF‐1 receptor (CSF‐1R) GM‐CSF blockade/depletion such subpopulations, both steady state during inflammation. In state, administration neutralizing anti‐CSF‐1R monoclonal antibody (mAb) rapidly (within...
Cigarette smoke is the major cause of chronic obstructive pulmonary disease (COPD), and there currently no satisfactory therapy to treat people with COPD. We have previously shown that granulocyte/macrophage colony-stimulating factor (GM-CSF) regulates lung innate immunity LPS through Akt/Erk activation nuclear factor-kappaB activator protein (AP)-1.The aim this study was determine whether neutralization GM-CSF can inhibit cigarette smoke-induced inflammation in vivo.Male BALB/c mice were...
Abstract Influenza A virus (IAV) infections are a common cause of acute exacerbations chronic obstructive pulmonary disease (AECOPD). Oxidative stress is increased in COPD, IAV-induced lung inflammation and AECOPD. Therefore, we investigated whether targeting oxidative with the Nox2 oxidase inhibitors ROS scavengers, apocynin ebselen could ameliorate mouse model Male BALB/c mice were exposed to cigarette smoke (CS) generated from 9 cigarettes per day for 4 days. On 5, infected 1 × 10 4.5...
Background Chronic Obstructive Pulmonary Disease (COPD) is currently the fifth leading cause of death worldwide. Neutrophilic inflammation prominent, worsened during infective exacerbations and refractory to glucocorticosteroids (GCs). Deregulated neutrophilic can excessive matrix degradation through proteinase release. Gelatinase azurophilic granules within neutrophils are a major source metalloproteinase (MMP)-9 neutrophil elastase (NE), respectively, which elevated in COPD. Methods...
M-CSF (or CSF-1) and GM-CSF can regulate the development function of mononuclear phagocyte system (MPS). To address some outstanding sometimes conflicting issues surrounding this biology, we undertook a comparative analysis effects neutralizing mAbs to these CSFs on murine MPS populations in steady-state during acute inflammatory reactions. CSF-1 neutralization, but not GM-CSF, normal mice rapidly reduced numbers more mature Ly6C(-) monocytes blood bone marrow, without any effect...