A5049203385- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cytokine Signaling Pathways and Interactions
- Adipose Tissue and Metabolism
- IL-33, ST2, and ILC Pathways
- Regulation of Appetite and Obesity
- Immune Response and Inflammation
- Adipokines, Inflammation, and Metabolic Diseases
- Influenza Virus Research Studies
- Neuropeptides and Animal Physiology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune Cell Function and Interaction
- Respiratory viral infections research
- Lung Cancer Treatments and Mutations
- Biochemical Analysis and Sensing Techniques
- Pediatric health and respiratory diseases
- Latin American and Latino Studies
- Neonatal Respiratory Health Research
- Respiratory Support and Mechanisms
- Helicobacter pylori-related gastroenterology studies
- Pancreatic function and diabetes
- T-cell and B-cell Immunology
- Travel-related health issues
- Hypothalamic control of reproductive hormones
- Pneumonia and Respiratory Infections
Boston University
2019-2020
Pfizer (United States)
2014-2018
Janssen (Belgium)
2015
The University of Melbourne
2005-2014
The University of Texas at Austin
2014
The Royal Melbourne Hospital
2005-2006
UNSW Sydney
2005-2006
The University of Queensland
2005
Boston Children's Hospital
1969
Harvard University
1969
Abstract The clinical response to influenza infection ranges from mild disease severe pneumonia and it remains unclear whether the inflammatory is protective or pathogenic. We have defined a novel role for neutrophils in ameliorating lung injury during infection, thereby limiting development of disease. Infection neutrophil-depleted mice with virus HKx31 (H3N2) led rapid weight loss, pneumonia, death. Neutropenia was associated enhanced replication respiratory tract; however, viral titers...
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 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...
Tumor cell proliferation and migration processes are regulated by multiple metabolic pathways including glycolysis de novo lipogenesis. Since acetyl-CoA carboxylase (ACC) is at the junction of lipids synthesis oxidative pathways, we investigated whether use a dual ACC inhibitor would provide potential therapy against certain lipogenic cancers. The impact ACC1/ACC2 inhibition was using as well siRNA knock down on cellular viability metabolism two glioblastoma multiform cancer lines, U87 more...
Abstract Visceral white adipose tissue (vWAT) expands and undergoes extensive remodeling during diet-induced obesity. Much is known about the contribution of various stromal vascular cells to process, but less changes that occur within adipocyte as it becomes progressively dysfunctional. Here, we performed a transcriptome analysis isolated vWAT adipocytes assess global pathway occurring in response chronic high fat diet (HFD). The data demonstrate responds HFD by adopting fibroblast-like...
The innate immune inflammatory response to lipopolysaccharide (LPS, an endotoxin) is essential for lung host defense against infection by gram-negative bacteria but also implicated in the pathogenesis of some diseases. Studies on genetically altered mice implicate granulocyte-macrophage colony-stimulating factor (GM-CSF) responses LPS; however, physiological effects GM-CSF neutralization are poorly characterized. We performed detailed kinetic and dose-response analyses inflammation LPS...
Rationale: Despite irrefutable epidemiologic evidence, cigarette smoking remains the major preventable cause of lung disease morbidity worldwide. The appetite-suppressing effect tobacco is a behavioral determinant smoking, but underlying molecular and neuronal mechanisms are not understood. Neuropeptide Y (NPY) an orexigenic neuropeptide, whose activity in hypothalamic paraventricular nucleus governs appetite.Objectives: To compare effects smoke exposure equivalent food restriction on body...
Please cite this paper as: Larcombe et al. (2011) Sexual dimorphism in lung function responses to acute influenza A infection. Influenza and Other Respiratory Viruses 5(5), 334–342. Background Males are generally more susceptible respiratory infections; however, there few data on the physiological such infections males females. Objectives To determine whether sexual exists physiological/inflammatory of weanling adult BALB/c mice influenza. Methods Weanling both sexes were inoculated with or...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Citrate is a key regulatory metabolic intermediate as it facilitates the integration of glycolysis and lipid synthesis pathways. Inhibition hepatic extracellular citrate uptake, by blocking sodium-coupled transporter (NaCT or SLC13A5), has been suggested potential therapeutic approach to treat disorders. NaCT transports from blood into cell coupled transport sodium ions. The studies herein report identification characterization novel small dicarboxylate molecule (compound 2) capable...
Abstract The etiology of asthma, a chronic inflammatory disorder the airways, remains obscure, although T cells appear to be central disease mediators. Lyn tyrosine kinase has been implicated as both facilitator and inhibitor signaling pathways that play role in allergic inflammation, its asthma is unclear because not expressed cells. We show present study Lyn−/− mice develop severe, persistent asthma-like syndrome with lung eosinophilia, mast cell hyperdegranulation, intensified...
Brown adipose tissue (BAT) plays a pivotal role in promoting energy expenditure by the virtue of uncoupling protein-1 (UCP-1) that differentiates BAT from its storing white (WAT) counterpart. The clinical implication "classical" (originates Myf5 positive myoblastic lineage) or "beige" fat through trans-differentiation WAT) activation improving metabolic parameters is now becoming apparent. However, inducers and endogenous molecular determinants govern lineage commitment differentiation...
Obesity and cigarette smoking are both important risk factors for insulin resistance, cardiovascular disease, cancer. Smoking reduces appetite, which makes many people reluctant to quit. Few studies have documented the metabolic impact of combined smoke exposure (se) high-fat-diet (HFD). Neuropeptide Y (NPY) is a powerful hypothalamic feeding stimulator that promotes obesity. We investigated how chronic se affects caloric intake, adiposity, plasma hormones, inflammatory mediators, NPY...
Interleukin (IL)-6 is a potent immunomodulatory cytokine that associated with emphysema, major component of chronic obstructive pulmonary disease (COPD). IL-6 signaling via the gp130 coreceptor coupled to multiple pathways, especially latent transcription factor signal transducer and activator (Stat)3. However, pathological role endogenous gp130-dependent Stat3 activation in emphysema ill defined. To elucidate IL-6/gp130/Stat3 axis cellular molecular pathogenesis we employed genetic...
Treatment with PPARγ agonists in vivo improves human adipocyte metabolism, but the cellular mechanisms and possible depot differences responsiveness to their effects are poorly understood. To examine ex metabolic of rosiglitazone (Rosi), we cultured explants visceral (omental) abdominal subcutaneous adipose tissues for 7 days. Rosi increased mRNA levels transcriptional regulators brite/beige adipocytes (PGC1α, PRDM16), triglyceride synthesis (GPAT3, DGAT1), lipolysis (ATGL) similarly from...
Summary Background The molecular determinants of the severity and persistence allergic asthma remain poorly understood. Suppressor cytokine signalling 1 (SOCS1) is a negative regulator IL‐4‐dependent pathways in vitro might therefore control T‐helper type 2 (Th2) immunity associated traits, such as IgE levels, mucin production, IL‐5 IL‐13 induction, eosinophilic mucosal inflammation, which are implicated asthma. Objective To investigate role SOCS1 regulating Th2‐associated disease traits...
Please cite this paper as: Wong et al. (2011) Oseltamivir treatment of mice before or after mild influenza infection reduced cellular and cytokine inflammation in the lung. Influenza Other Respiratory Viruses 5(5), 343–350. Background Lung is a critical determinant outcomes but seldom evaluated animal studies oseltamivir (OS), which have focused on viral titre survival. Objectives To study effects pre‐ post‐infection dosing with OS replication mouse model non‐lethal infection. Methods BALB/c...
While global success in cessation advocacy has seen smoking rates fall many developed countries, persistent lung inflammation ex-smokers is an increasingly important clinical problem whose mechanistic basis remains poorly understood. In this study, candidate effector mechanisms were assessed mice exposed to cigarette smoke (CS) for 4 months following from long term CS exposure. BALF neutrophils, CD4+ and CD8+ T cells innate NK remained significantly elevated cessation. Analysis of neutrophil...
Abstract In obesity, IL-13 overcomes insulin resistance by promoting anti-inflammatory macrophage differentiation in adipose tissue. Endogenous levels can be modulated the decoy receptor, IL-13Rα2, which inactivates and depletes cytokine. this study, we show that IL-13Rα2 is markedly elevated tissues of obese mice. Mice deficient had high expression response markers tissue, consistent with increased activity at baseline. Moreover, exposure to type 2 cytokine-inducing alarmin, IL-33, enhanced...
Neutrophilic lung inflammation is an essential component of host defense against diverse eukaryotic and prokaryotic pathogens, but in chronic inflammatory diseases, such as obstructive disease (COPD), severe asthma, cystic fibrosis, bronchiolitis, it may damage the host. Glucocorticosteroids are widely used these conditions their infectious exacerbations; however, clinical efficacy steroids disputed. In this study, we a proteomic approach to identify molecules contributing neutrophilic...
Obesity and cigarette smoking independently constitute major preventable causes of morbidity mortality obesity is known to worsen lung inflammation in asthma. Paradoxically, higher body mass index (BMI) associated with reduced induced COPD whereas low BMI increases risk. To date, no study has investigated the effect a dietary-induced smoke exposure on loss skeletal muscle mice. Male BALB/c mice were exposed 4 cigarettes/day, 6 days/week for 7 weeks, or sham handled. Mice consumed either...