S100 Proteins in asthma [ 2007 - 2009 ]

Research Grant

Researchers: E/Pr Carolyn Geczy (Principal investigator) ,  Dr Kenneth Hsu ,  Prof Paul Thomas

Brief description 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.

Funding Amount $AUD 561,978.39

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant