| Mechanisms and clinical relevance of TRAIL-triggered responses in synovial fibroblasts of rheumatoid arthritis patients. | |
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MedLine Citation:
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PMID: 21305500 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Studies in mice suggest a protective role for the TNF-related apoptosis-inducing ligand (TRAIL) in arthritis. We investigated the role of TRAIL in rheumatoid arthritis (RA) patients. METHODS: In the present study, we compared RA Fibroblast-like synoviocytes (FLS) resistant and RAFLS-sensible to TRAIL-induced apoptosis, including levels of the TRAIL receptors (TRAIL-R) and clinical features of respective patient. Furthermore, we evaluated TRAIL and its soluble decoy receptor osteoprotegerin (OPG) levels in RA patients, osteoarthritis (OA) and spondylarthritis (SpA). RESULTS: Sensitivity to TRAIL-induced apoptosis varied in FLS from different patients and disease severity of RA patients inversely correlated with susceptibility of FLS to TRAIL-induced apoptosis. TRAIL-sensitive cells expressed significantly lower levels of TRAIL-R1 and silencing of TRAIL-R1 increased TRAIL-induced apoptosis in RA FLS. TRAIL levels were elevated in the arthritic joints of patients with established RA and synovial fluids displayed elevated TRAIL levels compared to OA and SpA patients. A low ratio of the soluble decoy receptor OPG to TRAIL in sera of early RA patients at baseline was associated with a better evolution of disease activity, but high serum levels of TRAIL at follow-up were associated with joint damages. CONCLUSION: These findings suggest a dual role for TRAIL in RA and resistance of RA FLS to TRAIL-induced apoptosis is associated with a disease promoting activity of TRAIL in RA. |
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Authors:
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Rachel Audo; Flavia Calmon-Hamaty; Dominique Baeten; Angelique Bruyer; Bernard Combe; Michael Hahne; Jacques Morel |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-4 |
Journal Detail:
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Title: Arthritis and rheumatism Volume: - ISSN: 1529-0131 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 by the American College of Rheumatology. |
Affiliation:
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Institut de Génétique Moléculaire de Montpellier, CNRS, UMR5535, Montpellier, France; Université Montpellier 1, Montpellier, France; Université Montpellier 2, Montpellier, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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