Determine The Role Of The SAA-Macrophage Axis On Respiratory Pathogen Clearance In Smoke Exposure Related Lung Disease.
Funder
National Health and Medical Research Council
Funding Amount
$617,810.00
Summary
Direct or second hand exposure to tobacco smoke significantly increases your risk of acquiring a chest infection. Infants and elderly smokers are particularly susceptible. This will continue to be a major global problem as household smoke exposure remains high in developing countries and disadvantaged indigenous communities. We will investigate how smoke alters important immune cells that normally clear lung infections, which may lead to completely new ways of treating chest infections.
The Role Of Pulmonary Macrophages In The Pathogenesis Of An Acute Exacerbation Of Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$495,710.00
Summary
We will examine the role of lung defence cells, known as macrophages, in triggering the inflammation of acute severe asthma. The experimental work will use unique mouse models of mild chronic asthma and of an acute exacerbation of the illness, which have been developed in our laboratories. We will study the mechanisms of activation of the asthmatic response and assess whether treatment with drugs that suppress the function of macrophages can help to control steroid-resistant exacerbations.
DEFINING SUBPOPULATIONS OF PATHOGENIC MACROPHAGES UNDERLYING LUNG DISEASES
Funder
National Health and Medical Research Council
Funding Amount
$640,496.00
Summary
Chronic obstructive pulmonary disease (COPD) is a serious lung disease that afflicts over 1 million people in Australia and adenocarcinoma is a common fatal lung cancer; both are typically caused by cigarette smoking, and macrophage-rich inflammation is a hallmark feature. Macrophages can destroy lung tissue and promote cancer development. Herein we will identify and profile macrophage subpopulations that are associated with lung inflammation and cancer to identify therapeutic targets that may y ....Chronic obstructive pulmonary disease (COPD) is a serious lung disease that afflicts over 1 million people in Australia and adenocarcinoma is a common fatal lung cancer; both are typically caused by cigarette smoking, and macrophage-rich inflammation is a hallmark feature. Macrophages can destroy lung tissue and promote cancer development. Herein we will identify and profile macrophage subpopulations that are associated with lung inflammation and cancer to identify therapeutic targets that may yield novel intervention strategies.Read moreRead less
Interleukin-17A Promotes Cigarette Smoke-induced Lung Inflammation And Damage
Funder
National Health and Medical Research Council
Funding Amount
$650,590.00
Summary
Emphysema is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of emphysema and accounts for more than 95% of cases in industrialized countries. Cigarette smoke triggers cells in the lung to release substances which cause inflammation and "eat away" lung tissue. The aim of this project is to identify therapies to prevent and treat emphysema.
The Role Of Src Family Tyrosine Kinases In Inflammatory Lung Disease And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
We aim to learn why some people develop COPD, a serious lung disease, and adenocarcinoma, a common fatal lung cancer. COPD is mostly caused by cigarette smoke which induces lung inflammation. Lung inflammation, which involves macrophage activation, is a major cancer risk. Macrophages can destroy lung tissue, and they may promote cancer development. We will study the role of Src kinases, which can regulate macrophage activation, which may lead to new treatments for these diseases.
This project will examine new ways in which the major effector cells of allergic inflammation and asthma are regulated by novel S100 protein mediators. We find two natural proteins of the innate immune system, present in cells in the lungs of patients with acute asthma. These have apparently opposing activates: one, S100A12, activates mast cells to release mediators that trigger asthma attack. We will characterise how this proteins is regulated in eosinophils, key cells in asthma. Because mast c ....This project will examine new ways in which the major effector cells of allergic inflammation and asthma are regulated by novel S100 protein mediators. We find two natural proteins of the innate immune system, present in cells in the lungs of patients with acute asthma. These have apparently opposing activates: one, S100A12, activates mast cells to release mediators that trigger asthma attack. We will characterise how this proteins is regulated in eosinophils, key cells in asthma. Because mast cells reside in almost all body tissues and are also important mediators of host responses to allergy, infection and in chronic inflammation such as rheumatoid arthritis and psoriasis, our studies may indicate novel and unexpected ways in which they are activated. A second S100 protein (S100A8) is an efficient scavenger of oxidants that can cause damage to the lung. We find both S100A12 and S100A8 that has been modified by oxidants, in sputum from pateints with asthma. In addition to its anti-oxidant effects, S100A8 can downregulate production of some of the inflammatory mediators that promote allergy and asthma. This is an important finding that will help us understand how drugs used in treatment, such as steroids, are acting. We will generate a mouse expressing this protein in its lungs and determine how this affects normal lungs and the course of asthma. If, as we expect, asthma is reduced, we will have found a novel new pathway that is important in the resolution of asthma. Results from this project will provide new knowledge concerning mechanisms of regulation in allergy and asthma and may lead to the design of novel strategies to regulate the process. Results will have broader ramifications applicable to other chronc inflammatory where these proteins are expressed. We have new reagents that could also assist in the diagnosis of these conditions and may be useful for monitoring treatment.Read moreRead less