Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

INTRODUCTION: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a tumour necrosis factor (TNF) family member capable of inducing apoptosis in many cell types. METHODS: Using 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. RESULTS: Significantly 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. CONCLUSIONS: This 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.

Original publication

DOI

10.1186/ar2603

Type

Journal article

Journal

Arthritis Res Ther

Publication Date

2009

Volume

11

Keywords

Aged, Apoptosis, Arthritis, Rheumatoid, Caspase Inhibitors, Enzyme Inhibitors, Female, Gene Expression, Humans, Immunohistochemistry, In Situ Nick-End Labeling, Inhibitor of Apoptosis Proteins, Male, Microtubule-Associated Proteins, Middle Aged, Receptors, TNF-Related Apoptosis-Inducing Ligand, Reverse Transcriptase Polymerase Chain Reaction, Survivin, Synovial Membrane, TNF-Related Apoptosis-Inducing Ligand, X-Linked Inhibitor of Apoptosis Protein