In this study, mouse models of disease will be used to determine the mechanisms by which the proinflammatory molecule called MIFpromotes the development of insulin resisitance and type 2 diabetes. We will also test whether therapeutic blockade of MIF can prevent the progression of disease in mice with established type 2 diabetes. Studies on tissue samples obtained from human patients will be used to confirm the human relevance of these findings.
Macrophage Migration Inhibitory Factor (MIF) And P53 In Rheumatoid Arthritis .
Funder
National Health and Medical Research Council
Funding Amount
$333,055.00
Summary
Rheumatoid arthritis (RA) is an inflammatory disease affecting approximately 1% of the population. It is characterised by severe inflammation and destruction of joints resulting in significant health problems. The lining tissue of joints is known to be infiltrated by inflammatory cells. In addition to this infiltration of inflammatory cells, there is overgrowth of the normal lining cells of joints. These overgrowing cells contribute significantly to joint damage by invading cartilage and bone an ....Rheumatoid arthritis (RA) is an inflammatory disease affecting approximately 1% of the population. It is characterised by severe inflammation and destruction of joints resulting in significant health problems. The lining tissue of joints is known to be infiltrated by inflammatory cells. In addition to this infiltration of inflammatory cells, there is overgrowth of the normal lining cells of joints. These overgrowing cells contribute significantly to joint damage by invading cartilage and bone and allowing inflammatory cells to reach these areas. The abnormal growth of these cells has been related to the malfunction of certain genes that usually restrain abnormal growth. These genes called tumour suppressor genes are known to be damaged in joint lining cells derived from RA. The best known of these abnormal tumour suppressor genes is called p 53. The product of the p53 gene, the p 53 protein, is particularly important in slowing down the growth of cells. The applicant has recently shown that an inflammatory product called MIF is released in large quantities by joint lining cells in RA. Previous studies by the applicant have shown that blocking MIF using an antibody almost completely prevents arthritis development in a rat model. These studies indicate that MIF is likely to be an important contributor to disease in RA. Recent preliminary studies in the applicant s laboratory have shown that MIF can decrease p53 levels in joint lining cells from RA patients and also that MIF can increase the growth rate of these cells. These preliminary data indicate that MIF may contribute significantly to disease in RA by overriding control of normal cell growth by p53. Confirmation and full exploration of the regulation of p53 expression and function by MIF may highlight a novel way to treat the excessive growth and invasion by joint lining cells which characterises RA.Read moreRead less
Macrophage Migration Inhibitory Factor (MIF): Pathological And Therapeutic Significance In Post- Infarct Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$547,577.00
Summary
Ischemic heart injury mediated by the inflammatory response has a significant impact on the prognosis. MIF is a central factor mediating and amplifying the inflammatory response but its role in heart disease remains largely untested. This project will study, for the first time, the crucial role of MIF in ischemic heart disease and will establish important experimental evidence for developing new anti-inflammation therapeutic strategies against ischemic heart injury.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$583,477.00
Summary
Ross River virus and chikungunya virus cause muscle and joint pain that can persist for a long time. This project looks at factors in the human host that affect the disease severity, with the aim of finding new treatments.
We discovered, characterised and commercialised Macrophage inhibitory cytokine-1 (MIC-1/GDF15) for human therapy. Its blood level predicts death from cancer, heart attack/stroke and other diseases. This study will add important information for understandg the actions of this important protein