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

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-...

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Autores principales: Dharmapatni, Anak ASSK, Smith, Malcolm D, Findlay, David M, Holding, Christopher A, Evdokiou, Andreas, Ahern, Michael J, Weedon, Helen, Chen, Paul, Screaton, Gavin, Xu, Xiao N, Haynes, David R
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688245/
https://www.ncbi.nlm.nih.gov/pubmed/19171073
http://dx.doi.org/10.1186/ar2603
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author Dharmapatni, Anak ASSK
Smith, Malcolm D
Findlay, David M
Holding, Christopher A
Evdokiou, Andreas
Ahern, Michael J
Weedon, Helen
Chen, Paul
Screaton, Gavin
Xu, Xiao N
Haynes, David R
author_facet Dharmapatni, Anak ASSK
Smith, Malcolm D
Findlay, David M
Holding, Christopher A
Evdokiou, Andreas
Ahern, Michael J
Weedon, Helen
Chen, Paul
Screaton, Gavin
Xu, Xiao N
Haynes, David R
author_sort Dharmapatni, Anak ASSK
collection PubMed
description 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.
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spelling pubmed-26882452009-05-29 Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium Dharmapatni, Anak ASSK Smith, Malcolm D Findlay, David M Holding, Christopher A Evdokiou, Andreas Ahern, Michael J Weedon, Helen Chen, Paul Screaton, Gavin Xu, Xiao N Haynes, David R Arthritis Res Ther Research Article 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. BioMed Central 2009 2009-01-27 /pmc/articles/PMC2688245/ /pubmed/19171073 http://dx.doi.org/10.1186/ar2603 Text en Copyright © 2009 Dharmapatni et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Dharmapatni, Anak ASSK
Smith, Malcolm D
Findlay, David M
Holding, Christopher A
Evdokiou, Andreas
Ahern, Michael J
Weedon, Helen
Chen, Paul
Screaton, Gavin
Xu, Xiao N
Haynes, David R
Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium
title Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium
title_full Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium
title_fullStr Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium
title_full_unstemmed Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium
title_short Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium
title_sort elevated expression of caspase-3 inhibitors, survivin and xiap correlates with low levels of apoptosis in active rheumatoid synovium
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688245/
https://www.ncbi.nlm.nih.gov/pubmed/19171073
http://dx.doi.org/10.1186/ar2603
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