Novel mechanisms in regulating cytokine secretion in the inflammatory response

Funded Activity Summary

Macrophages are key cells in the immune and inflammatory response. They play a role in many biological processes including wound healing and resistance to tumours and infections. It is also a major cell involved in mediating inflammation and tissue damage in chronic inflammatory diseases such as atherosclerosis and rheumatoid arthritis. The macrophage's role in these processes is achieved in large part by secreting enzymes and other proteins called cytokines to the outside of the cell. These cytokines are synthesized by the macrophage and travel through a secretory pathway in the cell, in order to be released to the outside of the cell. There are various quality control mechanisms along the pathway which ensure only correctly made functional protein is secreted out of the cell. One cytokine, called macrophage inhibitory cytokine is produced by the immune cells called macrophages only when they become activated to mount an immune response against invading pathogens. The cell uses a novel mechanism to ensure the quality control of this cytokine. The propeptide of this cytokine targets incorrectly folded cytokine to a protein complex called the proteasome for degradation. This prevents secretion of inactive cytokine. Additionally, the propeptide of the cytokine helps secretion from macrophages by a novel mechanism. Because of these characteristics the cytokine provides a good model to study secretion from macrophages under pro- and anti-inflammatory conditions. In addition, demonstrating that activation of the macrophages causes a major upregulation in the synthesis and secretion of cytokines by novel mechanisms, will further our understanding of how the macrophage operates in fulfilling its role in the immune response.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $323,160.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Biochemistry And Cell Biology Not Elsewhere Classified

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

atherosclerosis | chronic inflammatory disease | cytokine secretion | ion channels | macrophage | proteasome and protein degradation | protein folding/trafficking in secretion | rheumatoid arthritis

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