Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synoviumReport as inadecuate




Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 11:R13

First Online: 27 January 2009Received: 20 June 2008Revised: 02 December 2008Accepted: 27 January 2009

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 pathways that lead to apoptosis. This inhibition of apoptosis was observed downstream of caspase-3 and may involve the caspase-3 inhibitors, survivin and xIAP.

AbbreviationsACRAmerican College of Rheumatology

CRPC-reactive protein

DAS28disease activity score 28

DMARDdisease modifying antirheumatic drug

ESRerythrocyte sedimentation rate

FADDFas associated death domain

FLIPflice inhibitory protein

IAPinhibitor of apoptosis protein

Igimmunoglobulin

OAosteoarthritis

OPGosteoprotegerin

PCRpolymerase chain reaction

RArheumatoid arthritis

RFrheumatoid factor

SpAspondyloarthropathies

SQAsemiquantitative analysis

TNFtumour necrosis factor

TRAILtumour necrosis factor related apoptosis inducing ligand

TUNELterminal deoxynucleotidyl transferase biotin-dUTP nick end labelling

xIAPx-linked inhibitor of apoptosis protein.

Electronic supplementary materialThe online version of this article doi:10.1186-ar2603 contains supplementary material, which is available to authorized users.

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Author: Anak ASSK Dharmapatni - Malcolm D Smith - David M Findlay - Christopher A Holding - Andreas Evdokiou - Michael J Ahern

Source: https://link.springer.com/







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