Abstract
IntroductionTumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a tumour necrosis factor (TNF) family member capable of inducing apoptosis in many cell types.MethodsUsing immunohistochemistry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) and real-time PCR we investigated the expression of TRAIL, TRAIL receptors and several key molecules of the intracellular apoptotic pathway in human synovial tissues from various types of arthritis and normal controls. Synovial tissues from patients with active rheumatoid arthritis (RA), inactive RA, osteoarthritis (OA) or spondyloarthritis (SpA) and normal individuals were studied.ResultsSignificantly higher levels of TRAIL, TRAIL R1, TRAIL R2 and TRAIL R4 were observed in synovial tissues from patients with active RA compared with normal controls (p < 0.05). TRAIL, TRAIL R1 and TRAIL R4 were expressed by many of the cells expressing CD68 (macrophages). Lower levels of TUNEL but higher levels of cleaved caspase-3 staining were detected in tissue from active RA compared with inactive RA patients (p < 0.05). Higher levels of survivin and x-linked inhibitor of apoptosis protein (xIAP) were expressed in active RA synovial tissues compared with inactive RA observed at both the protein and mRNA levels.ConclusionsThis study indicates that the induction of apoptosis in active RA synovial tissues is inhibited despite stimulation of the intracellular pathway(s) that lead to apoptosis. This inhibition of apoptosis was observed downstream of caspase-3 and may involve the caspase-3 inhibitors, survivin and xIAP.
Highlights
Tumour necrosis factor-related apoptosisinducing ligand (TRAIL) is a tumour necrosis factor (TNF) family member capable of inducing apoptosis in many cell types
This study indicates that the induction of apoptosis in active rheumatoid arthritis (RA) synovial tissues is inhibited despite stimulation of the intracellular pathway(s) that lead to apoptosis
Decreased apoptosis has been proposed as a possible factor that contributes to the hyperplasia of the synovial membrane and accumulation of inflammatory cells observed in the synovitis of patients with active rheumatoid arthritis (RA) [1,2]
Summary
Tumour necrosis factor-related apoptosisinducing ligand (TRAIL) is a tumour necrosis factor (TNF) family member capable of inducing apoptosis in many cell types. Decreased apoptosis has been proposed as a possible factor that contributes to the hyperplasia of the synovial membrane and accumulation of inflammatory cells observed in the synovitis of patients with active rheumatoid arthritis (RA) [1,2]. Inducing apoptosis in these synovial cells has the potential to reduce the disease severity and progression similar to that. The second type of TRAIL receptors act as decoy receptors and these are TRAIL R3 (DcR1, decoy receptor 1), TRAIL R4 (DcR2, decoy receptor 2) and osteoprotegerin (OPG) [10]
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