Proapoptotic Activity of a Monomeric Smac Mimetic on Human Fibroblast-Like Synoviocytes from Patients with Rheumatoid Arthritis

Lattuada, D.; Casnici, Claudia; Crotta, Katia; Seneci, Pierfausto; Corradini, C.; Truzzi, Marcello; Ingegnoli, Francesca; Marelli, O

doi:10.1007/s10753-014-0012-1

Cited by 14 publications

(13 citation statements)

References 28 publications

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“…IAPs can regulate apoptosis by directly binding to and preventing downstream effector functions of caspase 3, caspase 7 and caspase 9, thereby blocking the assembly of caspase 8 and caspase 10 155,156 . In response to a pro-apoptotic stimulus, the diablo homolog, mitochondrial (also known as second mitochondria-derived activator of caspases (Smac)) can be liberated from the mitochondria and translocate into the cytoplasm to block the anti-apoptotic activity of IAPs 157,158 .…”

Section: Extrinsic Pathway Of Apoptosis In Ramentioning

confidence: 99%

“…A number of compounds have been designed to mimic the structure of these molecules. Smac mimetics bind specifically to three IAPs, including E3 ubiquitin-protein ligase XIAP, Baculoviral IAP repeat-containing protein 2 (also known as C-IAP1) and Baculoviral IAP repeat-containing protein 3 (also known as C-IAP2) 155 . One such Smac mimetic downregulates XIAP, C-IAP1 and C-IAP2 and can induce cell death in apoptosis-resistant RA fibroblast-like synoviocytes, thereby implicating this molecule as a local therapeutic for RA 155 .…”

Section: Extrinsic Pathway Of Apoptosis In Ramentioning

confidence: 99%

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The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases

2016

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Rheumatoid arthritis affects nearly 1% of the world's population and is a debilitating autoimmune condition that can result in joint destruction. During the past decade, inflammatory functions have been described for signalling molecules classically involved in apoptotic and non-apoptotic death pathways, including but not limited to toll-like receptor signalling, inflammasome activation, cytokine production, macrophage polarization and antigen citrullination. In light of these remarkable advances in the understanding of inflammatory mechanisms of the death machinery, this review provides a snapshot of the available evidence implicating death pathways, especially within the phagocyte populations of the innate immune system, in the perpetuation of rheumatoid arthritis. Elevated levels of signalling mediators of both the extrinsic and intrinsic apoptotic as well as the autophagy death pathways are observed in the joints of patients with rheumatoid arthritis. Furthermore, in rheumatoid arthritis patients, risk polymorphisms are present in signalling molecules of the extrinsic apoptotic and autophagy death pathways. Although research into the mechanisms underlying these death pathways has made considerable progress, this review highlights areas where further investigation is particularly needed. This exploration is critical, as new discoveries in this field could lead to the development of novel therapeutic targets for rheumatoid arthritis and other rheumatic diseases.

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Section: Extrinsic Pathway Of Apoptosis In Ramentioning

confidence: 99%

Section: Extrinsic Pathway Of Apoptosis In Ramentioning

confidence: 99%

The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases

2016

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“…Lattuada D found that SMAC was associated with caspase 8 and caspase 3 activities, and induced signi cant apoptosis in all RA-FLS samples. In addition, SMAC signi cantly upregulated IGFBP-5, a protein involved in differentiation, apoptosis, and osteoblastic activation, so they included that SMAC may represent a new therapeutic approach to RA treatment 31 .…”

Section: Discussionmentioning

confidence: 99%

Using protein microarray reveals clinical correlation between self-perception of patient and the apoptosis-related proteins in rheumatoid arthritis

Wen

Liu

Jiang

et al. 2020

Preprint

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Abstract Background: The most severe effects of rheumatoid arthritis (RA) are loss of physical function, which may have a significant impact on self-perception of patient (SPP). However, the inherent relationship between SPP and the key proteins is not clear. The aim of this study was to get an insight into SPP of RA in connection with the the apoptosis-related proteins. Methods: We set out to investigate changes of the apoptosis-related proteins expression in the peripheral blood mononuclear cells (PBMCs) of RA. Additionally, we aimed to correlate the apoptosis-related proteins expression profiles with SPP and clinical indexes. To this end, we employed antibody microarrays of the the apoptosis-related proteins in PBMCs from four RA patients and seven healthy controls. We used bioinformatics to screen several the apoptosis-related proteins. To validate key protein candidates, we performed Enzyme linked immunosorbent assay (ELISA) on 30 RA patients and 30 healthy controls. Results: We found the expression of ten the apoptosis-related proteins (caspase3, CD40, SMAC, HSP27, HTRA, IGFBP-1, IGFBP-6, sTNF-R1, sTNF-R2, TRAILR-3) were significantly altered in PBMCs of RA patients. Receiver operating characteristic (ROC) curve analysis suggested that these ten the apoptosis-related proteins are potential biomarkers of RA. Spearman Correlation analysis and Logistic-regression analysis revealed that the 10 selected the apoptosis-related proteins correlated with SPP and clinical indexes. Conclusion: Therefore, we highlight some the apoptosis-related proteins may serve as potential biomarkers in prediction of SPP for RA patients, although the underlying mechanisms need to be further explored.

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“…In contrast, cellular IAP1 (cIAP1) and cellular IAP2 (cIAP2) are unable to directly inhibit caspases and instead promote prosurvival signaling from TNF receptor (TNFR)1 complex I and limit formation of the apoptosis-inducing TNFR1 complex II [193–195]. In response to pro-apoptotic stimuli, the second mitochondria-derived activator of caspases (Smac) can be liberated from the mitochondria into the cytoplasm to block the anti-apoptotic activity of IAPs [196, 197], and a number of compounds designed as therapeutic targets imitate the structure of these molecules (Smac mimetics) [191]. …”

Section: Programmed Cell Death Pathways In Dendritic Cells and Macmentioning

confidence: 99%

The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis

Tsai

Perlman

Cuda

2017

Clinical Immunology

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Systemic lupus erythematosus (SLE) is a chronic multi-factorial autoimmune disease initiated by genetic and environmental factors, which in combination trigger disease onset in susceptible individuals. Damage to the kidney as a consequence of lupus nephritis (LN) is one of the most prevalent and severe outcomes, as LN affects up to 60% of SLE patients and accounts for much of SLE-associated morbidity and mortality. As remarkable strides have been made in unlocking new inflammatory mechanisms associated with signaling molecules of programmed cell death pathways, this review explores the available evidence implicating the action of these pathways specifically within dendritic cells and macrophages in the control of kidney disease. Although advancements into the underlying mechanisms responsible for inducing cell death inflammatory pathways have been made, there still exist areas of unmet need. By understanding the molecular mechanisms by which dendritic cells and macrophages contribute to LN pathogenesis, we can improve their viability as potential therapeutic targets to promote remission.

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Proapoptotic Activity of a Monomeric Smac Mimetic on Human Fibroblast-Like Synoviocytes from Patients with Rheumatoid Arthritis

Cited by 14 publications

References 28 publications

The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases

The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases

Using protein microarray reveals clinical correlation between self-perception of patient and the apoptosis-related proteins in rheumatoid arthritis

The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis

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