Several studies have reported on the importance 17-DMAG Phase 2 of TRAIL and TRAIL receptor expression in inducing or inhibiting apoptosis. Some studies have shown that TRAIL and its Inhibitors,Modulators,Libraries recep tor, TRAIL Inhibitors,Modulators,Libraries R2, are expressed in the synovial tissues of RA patients and TRAIL R2 is highly expressed in synovial cells in culture. TRAIL gene therapy Inhibitors,Modulators,Libraries has been reported to inhibit development of arthritis in a collagen induced mouse model. In addition, an agonistic monoclonal antibody that binds to the TRAIL death receptor, TRAIL R2, has been reported to induce apoptosis in RA synovial fibroblasts. However, none of the studies comprehensively inves tigated TRAIL and all its receptors in the synovial tissue from patients with various types of arthritis.

In addition to TRAIL and its receptor interaction, recent evi dence suggests that intracellular regulators such as FLIP, cas pases, members of the Bcl2 family and tumour suppressor proteins such as p53 are often central in determin ing whether apoptosis occurs in particular cells. Recently, survivin, a member of the IAP family, has been Inhibitors,Modulators,Libraries reported to be elevated in serum in RA, with high levels correlating with joint erosion in active RA. Many of the previous studies have focused on investigating the expression of TRAIL and TRAIL receptors using synovial fibroblasts in culture. However, this population of cells may not be representative of the inflammatory cells, such as lymphocytes and cells of the macrophage monocyte lineage. Therefore, the present study investigated the expres sion of TRAIL and each of the TRAIL receptors in synovial tis sues in situ from a range of arthritic conditions, including RA and OA.

The expression of intracellular pro and anti apoptotic molecules was simultaneously investigated with the extent of apoptosis in pathogenic and normal human synovial tissues. Materials and methods Patients and tissue preparation Synovial tissue samples were obtained from patients Inhibitors,Modulators,Libraries at the time of knee arthroscopy or total knee replacement at the Rheumatology unit at the Repatriation General Hospital, Adelaide, South Australia. Normal synovial tissues were obtained from patients attending sports medicine clinics with unexplained knee pain. All patients with active RA or spondyloarthropathy had active joint inflammation. Patients with inactive RA were in remission after successful disease Palbociclib clinical trial modifying antirheumatic drug treatment for active RA and were undergoing a further knee joint arthros copy for routine follow up. Informed consent was obtained from the patients before the procedures and the study was approved by the Repatriation General Hospital Human Ethics Committee. All patients diag nosed with RA fulfilled the 1987 revised criteria of the Ameri can College of Rheumatology.