Expression And Functions Of Leukocyte Immunoglobulin-like Receptor (LIR)-6 And LIR-4 In Inflammatory Arthritis (IA).
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Rheumatoid arthritis (RA) that affects millions worldwide is characterised by uncontrolled activation of immune cells destroying ones own joints. The reasons for this excessive activation of cells are not known and existing treatments are limited to easing symptoms. We will study the role of new proteins named as Leucocyte Ig-like Receptors in regulating immune cell activation. Understanding mechanisms that control unwanted activation of immune cells is critical in preventing and treating RA.
Characterisation Of The Anti-inflammatory Properties Of The N-3 Fatty Acid Product, 4-hydroxy-hexenal.
Funder
National Health and Medical Research Council
Funding Amount
$524,559.00
Summary
A concerted effort is being made by experts in the field of omega 3 fats (fish oils) to make specific recommendation on their use to improve human health . We have reasoned that the characterisation of a major oxidation product of these oils could be a key to understanding how these fats benefit us. The project is likely to influence the formulation of fish oils to enhance their health promoting properties.
Novel Roles For IL-33 In The Maintenance Of Bone Mass And As A Locally Derived Anabolic Factor For Bone
Funder
National Health and Medical Research Council
Funding Amount
$592,574.00
Summary
Over 10% of the population have thin, brittle bones that fracture easily, and is often seen in elderly people. When diagnosed, a fracture has usually already occurred and the bone is already thin. Drugs are available to stop further bone weakening, but building new bone would be best. We have found a protein in bone that reduces bone loss and stimulates bone formation processes. This project seeks to determine how this protein works and how to exploit it to design new bone building therapies.
A type of white blood cell, the macrophage, is a key player in determining the chronicity of inflammatory conditions such as rheumatoid arthritis, atherosclerosis, psoriasis, nephritis, multiple sclerosis etc. Two particular proteins can control macrophage development and functions, both under normal conditions and during inflammation. The project aims to understand this control. More rational ways to suppress inflammation due to aberrant macrophage function should result.
The Role Of The Plasminogen Activators (PAs), Urokinase-PA And Tissue-type PA In Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Many diseases, such as rheumatoid arthritis (RA), are inflammatory by nature. Intra-articular fibrin deposition is an early and persistent hallmark of inflammatory responses, resulting from an altered balance between coagulation (the production of fibrin) and fibrinolysis (the breakdown of fibrin). This fibrin accumulation can have adverse effects in RA, including mediating and-or enhancing inflammation, and contributing to subsequent joint damage. The plasminogen activators (PA), urokinase PA ( ....Many diseases, such as rheumatoid arthritis (RA), are inflammatory by nature. Intra-articular fibrin deposition is an early and persistent hallmark of inflammatory responses, resulting from an altered balance between coagulation (the production of fibrin) and fibrinolysis (the breakdown of fibrin). This fibrin accumulation can have adverse effects in RA, including mediating and-or enhancing inflammation, and contributing to subsequent joint damage. The plasminogen activators (PA), urokinase PA (u-PA) and tissue-type PA (t-PA) convert plasminogen into plasmin which can then breakdown the accumulated fibrin. Their presence in RA patients would therefore be beneficial. However, u-PA is also implicated in cell migration leading to inflammatory cells accumulating in the joint, and cartilage destruction, both of which are detrimental to disease outcome. In the joints of RA patients there are high levels of u-PA and low levels of t-PA. We, and our collaborators, have found that in the absence of t-PA, disease is exacerbated, whilst in the absence of u-PA, the outcome depends on the type of disease, either exacerbating or ameliorating disease. This highlights the different roles u-PA can have. The current proposal aims to determine the role of u-PA in inflammation and arthritis, and whether enhancing t-PA can have beneficial outcomes with respect to disease severity. In addition, we will also study whether intra-articular fibrin deposition can, in fact, drive the inflammatory reaction and cartilage destruction seen in RA. The findings will be important for our understanding of the role of fibrin accumulation in the inflammatory and destructive processes that occur in RA, and the roles of u-PA and t-PA in enhancing and preventing them respectively. Information gained will provide clues for useful strategies for the treatment of human inflammatory diseases, including RA.Read moreRead less
There is an unmet need for safe and effective anti-inflammatory drugs. Because P38 MAPK intracellular signalling modulates multiple pro-inflammatory cytokine actions, it appears to be an ideal candidate pathway. P38 inhibitors have been limited by their toxicity within hepatocytes. The aim of this program therefore is to develop agents with enhanced P38 MAPK inhibitory effects as well as reduced liver toxicity based on known structure activity relationships.
MIF Regulation Of MKP-1 And Glucocorticoid Responses In RA
Funder
National Health and Medical Research Council
Funding Amount
$398,156.00
Summary
Rheumatoid arthritis (RA) is a common chronic inflammatory disease which affects 1% of Australians. Up to 70% of patients are treated with 'steroids', which are drugs with major side effects. Recent research has shown that sensitivity to steroids is controlled by a number of natural proteins, and that balance between these proteins controls the effectiveness of steroids. The proposed research will define the interactions between these proteins.