Therapeutic Potential Of The IL-3-IL-5-GM-CSF Common Beta Receptor To Treat Upper And Lower Allergic Airway
Funder
National Health and Medical Research Council
Funding Amount
$150,442.00
Summary
This research aims to develop new treatments for allergic diseases such as asthma and allergic rhinitis, which remain significant public health problems in Australia. We will develop new therapies with the potential to completely suppress acute and chronic allergic disease targeting a common receptor protein that controls multiple facets of allergic inflammation. We will test antibodies intended to treat human asthma using a novel mouse strain expressing the human form of this receptor.
The Role Of Glutathione Transferase P1 In Regulating Allergic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$436,882.00
Summary
Recent studies have shown that a single amino acid change in an enzyme called glutathione tranferase Pi (GSTP)1 protects against the likelihood of developing asthma. This enzyme is found in the cells that line the airways and detoxifies harmful chemicals such as those found in pollutants and cigarette smoke. The aim of our study is to understand how GSTP1 protects against the development of asthma.
Inhibition Of Allergic Airway Inflammation By Nanoparticles
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Inhaled air pollution particulate matter causes asthma exacerbations, with 'ultrafine' nanoparticles thought to play a major role. Unexpectedly, we recently found that, by contrast, administration of inert ultrafine nanoparticles prevents allergic airway inflammation. We will identify the key particle physical and chemical properties associated with this novel type of disease inhibition, study particle effects in clinically-relevant disease models and identify mechanisms of action.
Role Of Zinc In The Respiratory Epithelium And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example ....This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example, asthma affects 12% of adults and amongst these, 15% waken weekly or more often with their asthma while 6% are hospitalized annually. There is a need to understand the basic mechanisms underlying these diseases so that new strategies can be developed to modify bronchocondtriction and inflammation. The project will provide new knowledge concerning the physiology of Zn in the respiratory epithelium and interactions between Zn deficiency and oxidants on injury in the respiratory tract. The usefulness of easily accessible nasal epithelial cells as a measure of Zn and Zn transporter levels deeper in the respiratory tract will be assessed. The project encompasses a number of fields and utilizes in vitro cellular and animal models, as well as tissues from human subjects.Read moreRead less
Fetomaternal Immunological Interactions In The Aetiology Of Allergic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$195,990.00
Summary
There is accumulating evidence that immune abnormalities that lead to allergy are present at birth, and may be linked with maternal factors in pregnancy. This study examines how immune interactions between the fetus and the mother during pregnancy predispose to allergic immune responses in the infant. Allergic diseases result from inappropriate Type 2 responses to the environment whereas Type 1 response dominate immune responses of nonallergic people. Type 2 immune responses are first initiated ....There is accumulating evidence that immune abnormalities that lead to allergy are present at birth, and may be linked with maternal factors in pregnancy. This study examines how immune interactions between the fetus and the mother during pregnancy predispose to allergic immune responses in the infant. Allergic diseases result from inappropriate Type 2 responses to the environment whereas Type 1 response dominate immune responses of nonallergic people. Type 2 immune responses are first initiated before birth when they are actually normal for fetal survival. In normal infants maturation of Type 1 immune responses plays a central role in switching off the Type 2 responses of fetal life. Allergic disease appears to be due to abnormal persistence of this Type 2 response pattern beyond the newborn period. One of the most striking abnormalities in allergic individuals is immature Type 1 function at birth. With rising rates of allergy, there is an urgent need to identify how the balance of Type 1 and Type 2 responses is regulated during this early period. Maternal factors appear to play a critical role. There is already evidence that Type 1 responses are lower in babies of allergic mothers compared to babies of allergic fathers, suggesting direct effects of the mother in pregnancy. Although pregnancy normally favours Type 2 immunity, there appears to be normal variation in the balance of Type 1 and Type 2 responses in pregnancy. We plan to determine if variations in this balance affect the fetal capacity for Type 1 responses. We propose that minor degrees of tissue mismatch (present in all pregnancies) will activate low grade Type 1 responses and enhance maturation of fetal Type 1 responses. We will determine if allergic mothers (prone to stronger Type 2 responses) have less developed Type 1 responses in pregnancy and if this plays a direct role in abnormal Type 1 responses observed in their babies.Read moreRead less
Initiating Events In The Development Of Allergic Airway Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$452,545.00
Summary
Despite recent advances we still do not understand the basic mechanisms which underlie the development of allergic airway inflammatory diseases such as rhinitis and asthma. It has been previously shown that when pollen are exposed to water they release a large number of very small starch granules which contain a number of potent allergens as well as plant steroids. In addition house dust mite allergens which are strongly associated with asthma are mostly located in small faecal pellets. Both the ....Despite recent advances we still do not understand the basic mechanisms which underlie the development of allergic airway inflammatory diseases such as rhinitis and asthma. It has been previously shown that when pollen are exposed to water they release a large number of very small starch granules which contain a number of potent allergens as well as plant steroids. In addition house dust mite allergens which are strongly associated with asthma are mostly located in small faecal pellets. Both these particles are ideally sized to enter the respiratory tract and initiate inflammatory responses. We have shown that these responses appear to be of the type that is needed to initiate allergic reactions. We intend to further study the interactions of these small inhaled allergen containing particles with cells of the respiratory tract. In this proposal we will look at both alveolar macrophages and respiratory epithelial cells. These approaches will not only provide new information about the processes of airway inflammation caused by allergens but may also define new therapeutic approaches to the treatment of these diseases.Read moreRead less
Effects Of Enteric Microflora On Mucosal And Systemic Immune Development In Infants At Risk Of Allergic Disease
Funder
National Health and Medical Research Council
Funding Amount
$219,750.00
Summary
The increase in allergic diseases over the last 20-30 years has been attributed to an increased immunological propensity to Type-2 allergic immune responses in the postnatal period. It has been proposed that this may be due to a relative deficiency of counter-regulatory Type 1 immune responses in early life. Thus, there is growing interest in factors that might affect Type 1 maturation in this early period. It has been proposed that progressively cleaner societies may have more allergies because ....The increase in allergic diseases over the last 20-30 years has been attributed to an increased immunological propensity to Type-2 allergic immune responses in the postnatal period. It has been proposed that this may be due to a relative deficiency of counter-regulatory Type 1 immune responses in early life. Thus, there is growing interest in factors that might affect Type 1 maturation in this early period. It has been proposed that progressively cleaner societies may have more allergies because there is less stimulation of the Type 1 responses during immune development. Bacterial products provide important maturation signals to the developing immune system, and may favour Type 1 responses. The largest early exposure to bacteria in occurs in the human gut, which is colonised with bacteria soon after birth. These bacteria play an important role in maintaining health, both in the protection from harmful bacteria, and in the development of food tolerance. There is evidence that infants in cleaner sociaeties may have alterations in bowel flora. For many years probiotic formulations (containing strains of these healthy bacteria) have been used safely to treat children with gastroenteritis to reduce the duration of diarrhoea. More recently it has been suggested that these formulations have a role in treating and even preventing allergic disease. Further research is needed to confirm this, and to define the underlying immunological processes. This randomised double blind control study will determine if supplementation with probiotic flora (in late pregnancy and in early infancy) can favourably influence gut colonisation, alter subsequent immune development, and help prevent allergic disease in infants at high risk (from allergic families).Read moreRead less