Rheumatoid synovial fluid T cells are sensitive to APO2L/TRAIL

Martínez‐Lorenzo, María José; Anel, Alberto; Saez-Gutierrez, Berta; Royo-Cañas, María; Bosque, Alberto; Álava, María Á.; Piñeiro, Andrés; Asín-Ungría, Jaime; Larrad, Luis

doi:10.1016/j.clim.2006.07.007

Cited by 39 publications

(42 citation statements)

References 44 publications

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“…Furthermore, in vitro studies revealed that TRAIL is able to control autoreactive B cell and T cell responses in mice (5). In line with this is a report that synovial fluid T cells from patients with RA are sensitive to TRAIL-induced apoptosis (15)(16)(17). Reports on the effect of TRAIL on RA FLS are controversial.…”

Section: Discussionsupporting

confidence: 61%

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Mechanisms and clinical relevance of TRAIL‐triggered responses in the synovial fibroblasts of patients with rheumatoid arthritis

Audo¹,

Calmon-Hamaty²,

Baeten³

et al. 2011

Arthritis & Rheumatism

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Objective. Results of studies in mice suggest a protective role for TRAIL in arthritis. The aim of this study was to investigate the role of TRAIL in patients with rheumatoid arthritis (RA).Methods. In the present study, we compared RA fibroblast-like synoviocytes (FLS) that were resistant or sensitive to TRAIL-induced apoptosis and the expression of TRAIL receptors in these cells, and also investigated the clinical features of the patients from whom the FLS were derived. Furthermore, we evaluated the levels of TRAIL and its soluble decoy receptor osteoprotegerin (OPG) in patients with RA, patients with osteoarthritis (OA), and patients with spondylarthritis (SpA).Results. Sensitivity to TRAIL-induced apoptosis varied in FLS from different patients, and the severity of disease in patients with RA was inversely correlated with the susceptibility of their FLS to TRAIL-induced apoptosis. TRAIL-sensitive cells expressed significantly lower levels of TRAILR-1, and silencing of TRAILR-1 increased TRAIL-induced apoptosis in RA FLS. TRAIL levels were elevated in the arthritic joints of patients with established RA, and TRAIL levels in the synovial fluid of these patients were elevated compared with levels in the synovial fluid of patients with OA or SpA. At baseline, a low OPG-to-TRAIL ratio in the sera of patients with early RA was associated with a better evolution of disease activity, but high serum levels of TRAIL at followup were associated with joint damage.Conclusion. These findings suggest that TRAIL has a dual role in RA, and that the resistance of RA FLS to TRAIL-induced apoptosis is associated with a disease-promoting activity of TRAIL in RA.

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Section: Discussionsupporting

confidence: 61%

“…This indicates activity of TRAIL in the synovium of patients with RA in spite of the presence of relatively high OPG concentrations. This concurs with a study by Martinez-Lorenzo et al demonstrating that the synovial fluid of patients with RA contains bioactive TRAIL (25).…”

supporting

confidence: 79%

Mechanisms and clinical relevance of TRAIL‐triggered responses in the synovial fibroblasts of patients with rheumatoid arthritis

Audo¹,

Calmon-Hamaty²,

Baeten³

et al. 2011

Arthritis & Rheumatism

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“…Furthermore, in vitro, TRAIL inhibited DNA synthesis and prevented lymphocyte cell cycle progression. Thus, unlike other members of the TNF superfamily, TRAIL is a prototype inhibitory cytokine that prevents autoimmune inflammation by inducing apoptosis and blocking cell cycle progression (Song et al, 2000;Liu et al, 2003;LamhamediCherradi et al, 2003;Yao et al, 2006;Martínez-Lorenzo et al, 2007). These findings suggest that systemically administered TRAIL represents a potential therapeutic strategy for the treatment of RA.…”

mentioning

confidence: 91%

Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on the Reduction of Joint Inflammation in Experimental Rheumatoid Arthritis

Jin

Chae²,

Kim³

et al. 2009

J Pharmacol Exp Ther

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This study focused on the potential therapeutic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on collagen-induced arthritis (CIA) and on the elucidation of the mechanisms involved. DBA/1J mice with established CIA were treated with various amount of recombinant soluble human TRAIL. The effects of TRAIL on the development and severity of CIA in this DBA/1J mouse model were assessed clinically and histologically, and a detailed investigation was conducted on proinflammatory cytokine and anticollagen-specific antibody levels. Cellular immunity was evaluated by investigating the proliferative responses and cytokine release profiles of splenocytes after TRAIL treatment. TRAIL treatment significantly reduced the severity and incidence of CIA, joint swelling, erythema, and edema. Histologic evaluations revealed that inflammatory cell infiltration, cartilage destruction, and bone erosion were significantly reduced in joints of TRAIL-treated mice with dose-dependent manner. TRAIL treatment also strongly decreased and/or normalized the productions of proinflammatory cytokines and of anti-collagen-specific antibodies in the sera of CIA mice. Furthermore, in vitro studies with primary splenocytes showed the cytotoxic effect of TRAIL on activated lymphocytes, with reduction of inflammatory cytokine release. These findings show that TRAIL administration is an effective anti-inflammatory treatment that prevents the development and progression of CIA in DBA/1J mice, and they suggest that TRAIL might be considered a potential treatment for human RA.

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“…In the third study, Pundt et al [46] showed that highly proliferating human RASF were less sensitive to exogenous TRAIL (as well as FasL) than RASF with decreased proliferation, suggesting that TRAILmediated stimulation of RASF proliferation could be dependent on other cell cycle factors that regulate the sensitivity of RASF to TRAIL, and even FasL for that matter. Fourth, TRAIL levels in T-cells recovered from RA synovial fluid were compared to TRAIL levels from T-cells recovered from the synovial fluid of patients with traumatic arthritis [47]. Although the synovial fluid T-cells from the RA patients were resistant to FasL-induced apoptosis, they were more sensitive to rTRAIL-induced apoptosis than synovial fluid T-cells from the traumatic arthritis patients.…”

Section: Trailmentioning

confidence: 99%

Apoptosis Resistance in Rheumatoid Arthritis Synovial Tissue

Malemud¹

2012

J Clin Cell Immunol

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Rheumatoid synovial fluid T cells are sensitive to APO2L/TRAIL

Cited by 39 publications

References 44 publications

Mechanisms and clinical relevance of TRAIL‐triggered responses in the synovial fibroblasts of patients with rheumatoid arthritis

Mechanisms and clinical relevance of TRAIL‐triggered responses in the synovial fibroblasts of patients with rheumatoid arthritis

Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on the Reduction of Joint Inflammation in Experimental Rheumatoid Arthritis

Apoptosis Resistance in Rheumatoid Arthritis Synovial Tissue

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