Mechanisms of inflammation by S100A12

Funded Activity Summary

This project will characterise the biological and functional properties of a novel human pro-inflammatory S100 protein. The protein is a natural component of the innate immune system and is regulated in cells by mediators of inflammation and infection. Our preliminary experiments indicate that this protein can activate mast cells. These cells reside in almost all body tissue and are located close to blood vessels and nerves. This location makes them prime targets to trigger vascular and inflammatory events. They are known to be important in allergy and infection and have a proposed role in chronic inflammatory processes. Although the mechanisms of mast cell activation contributing to acute responses in allergic reactions are well accepted, ways in which they are activated in asthma and other chronic inflammatory disease are virtually unknown. We will use lung biopsies from patients with asthma to detect patterns of expression of the protein and determine its effects on lung mast cells. A murine model will be used to define the characteristics of inflammation induced by the S100 protein and the role of mast cells in this process. Structural studies will define the parts of the protein necessary for mast cell activation. We will attempt to identify its receptor on mast cells to enable future studies to define how the protein triggers the cells to produce mediators such as histamine and those causing blood vessel changes. This knowledge could lead to design of novel drugs that could regulate this process. Results from this project will provide new knowledge of chronic inflammatory processes and could result in designing novel strategies to regulate these. Studies are relevant to infectious diseases and many other conditions with a chronic inflammatory basis, including asthma, rheumatoid arthritis, cardiovascular disease, cystic fibrosis and infection.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $392,036.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Pathology

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Asthma, rheumatoid arthritis, atherosclerosis | Chronic inflammatory diseases and infection | Identification of an S100 receptor on mast cells | Mechanisms of leukocyte recruitment | Novel mechanisms of mast cell activation | Pro-inflammatory properties of an S100 protein | Sepsis, cystic fibrosis

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