Grant: Operating Grant

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is characterized by eventual degradation of the articular cartilage and the subchondral bone. Cells of the synovial tissue (fibroblast-like synoviocytes and monocytes) and the synovial fluid of RA patients are immunologically highly active in that they express high levels of major histocompatibility complex (MHC) class II molecules, and contribute directly to tissue and joint destruction by their synthesis of various inflammatory mediators. A complete understanding of the factors controlling the local synthesis of these mediators in the rheumatoid joint is fundamental to understand the pathogenesis of the disease, and to provide new avenues for therapeutic intervention. Our in vitro studies clearly indicated that stimulation of activated fibroblast-like synoviocytes and monocytes of RA patients with mycoplasma arthritiditis-derived mitogen (named as MAM), a molecule that is secreted by mycoplasma arthritiditis, leads to the production of various inflammatory mediators. These mediators play an important role in initiating and or progressing RA disease. Athough we thought that the MAM-induced response is mainly mediated through MHC class II molecules, recent evidence suggest the involvement of other receptors. Therefore, we propose these studies to investigate the involvement of different MAM receptors in initiating and developing the disease, and study the possible modulation of the disease using different forms of modified MAM.