Activated Protein C Suppresses The Abnormal Immune Response In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
This project will determine whether activated protein C (APC) reduces the severity of rheumatoid arthritis (RA) by altering the abnormal response of a type of white blood cells known as the T cells. Experiments will utilise T cells isolated from patients with RA, normal controls and an animal model of RA, to examine a newly discovered immune pathway now thought to play a major role in causing RA. The results will help clarify whether and how APC prevents joint destruction in RA
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.
Longitudinal Studies Of Knee Osteoathritic Changes Using Magnetic Resonance Imaging (MRI)
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
The associations between MRI-assessed knee structural changes and radiographic changes over 5 years in older people will be determined. The effects of physical activity in adults and childhood, and the roles of inflammation will be described. The study represents a cost-effective comprehensive approach to osteoarthritis, a major public health problem, and is a natural progression of previous work that supports the objectives of the Bone and Joint Decade and addresses a national health priority.
The Role Of Specific Innate And Adaptive Immune System Components In Regulating Viral-induced Arthritis-arthralgia
Funder
National Health and Medical Research Council
Funding Amount
$402,767.00
Summary
Many viruses are known to cause arthritis (e.g. HIV, hepatitis viruses, mosquito borne viruses). Symptoms of viral arthritis include joint pain, stiffness, and swelling. The mechanism of disease is poorly understood. We have developed a novel animal model of disease by which to study arthritic disease caused by viral infections. This model provides an excellent opportunity to explore the mechanisms of rheumatic disease in a complete functioning animal and to explore new treatment regimes.
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.
Predictors Of The Outcomes For Joint Inflammation And Damage In Recent Onset Rheumatoid Arthritis Patients
Funder
National Health and Medical Research Council
Funding Amount
$255,750.00
Summary
Currently, it is difficult to predict what will happen to an individual patient who presents with newly diagnosed rheumatoid arthritis, either as a result of the natural history of the disease or as a result of drug treatment. It is also difficult to decide which drug treatment to offer a patient and when to decide to change the treatment to obtain a better clinical response. This study will investigate whether it is possible to predict the outcomes for a particular patient with rheumatoid arthr ....Currently, it is difficult to predict what will happen to an individual patient who presents with newly diagnosed rheumatoid arthritis, either as a result of the natural history of the disease or as a result of drug treatment. It is also difficult to decide which drug treatment to offer a patient and when to decide to change the treatment to obtain a better clinical response. This study will investigate whether it is possible to predict the outcomes for a particular patient with rheumatoid arthritis for joint inflammation and joint destruction, based on the findings in the joint lining tissue. This study will also investigate whether it is possible to make decisions on the likely success of drug treatment given to a patient with rheumatoid arthritis based on the initial or subsequent joint lining tissue biopsies. If successful, this study will lead to a greater ability to advise patients about likely outcomes from their condition, either with or without treatment and also to predict whether a treatment is likely to work at an early stage. In addition, this study may identify future potential treatments for rheumatoid arthritis.Read moreRead less
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
Role Of The Novel TGF-b Superfamily Cytokine MIC-1 In The Pathogenesis And Treatment Of Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$309,536.00
Summary
Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important family of proteins that are involved in wound healing, development and inflammation. Our data thus far suggests that MIC-1 is an anti-inflammatory factor that is of particular relevance in rheumatoid arthritis. We wish to determine the relationship between the amount of this cytokine in the ....Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important family of proteins that are involved in wound healing, development and inflammation. Our data thus far suggests that MIC-1 is an anti-inflammatory factor that is of particular relevance in rheumatoid arthritis. We wish to determine the relationship between the amount of this cytokine in the joint and the blood and the activity of rheumatoid arthritis. To better understand the actions of this molecule, we also want to study the factors that regulate the production of MIC-1 from human blood cells. Finally, to assess whether MIC-1 is useful for the treatment of rheumatoid arthritis, we will use gene therapy approaches to develop animals that produce increased amounts of MIC-1 and determine whether this prevents or mitigates the development of rheumatoid arthritis.Read moreRead less