Smac127 Has Proapoptotic and Anti-Inflammatory Effects on Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Lattuada, D.; Gualtierotti, Roberta; Crotta, Katia; Seneci, Pierfausto; Ingegnoli, Francesca; Corradini, C.; Viganò, Roberto; Marelli, O; Casnici, Claudia

doi:10.1155/2016/6905678

Cited by 6 publications

(4 citation statements)

References 36 publications

(43 reference statements)

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“…At the molecular level, synovial fibroblasts are characterized by the activation of signaling cascades that result in the inhibition of apoptosis (Khan et al, 2011). In agreement with these results, Lattuada et al (2016) proved that the percentage of apoptotic cells (RA-FLSs) cultured in synovial fluid samples aspirated from the joints of RA was lower than in cells cultured in tissue medium alone, probably because of the presence in the SF of anti-apoptotic factors. Resistance to apoptosis in RA-FLSs depends on up regulation of IAPs which are expressed at high levels in RA-FLSs (Casnici et al, 2014).…”

Section: Discussionsupporting

confidence: 66%

Evaluation of the effect of vitamin C on caspase 9 and oxidative stress in rheumatoid arthritis patients

Elshamy¹,

Gaafar²,

ElAshwah³

et al. 2018

Afr. J. Biochem. Res.

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Rheumatoid arthritis (RA) is a chronic and an autoimmune disease of the joints and is widely distributed worldwide. It is characterized by alterations of the antioxidant defense system and increased free radical formation and pro-inflammatory cytokine. The aim of the present study was to evaluate the effect of vitamin C supplementation on oxidative stress biomarkers and caspase 9 level in rheumatoid arthritis patients. This study included 30 RA patients and 30 healthy subjects. Plasma levels of malondialdehyde (MDA), total antioxidant capacity (TAC), caspase 9 and 8-hydroxy-2′deoxyguanosine (8 OHdG) were assayed as well as blood vitamin C level. These parameters were reevaluated in RA patients after vitamin C supplementation for one month. Increased MDA and 8 OHdG levels and reduced TAC, caspase 9 and vitamin C. Levels were demonstrated in RA patients. After vitamin C supplementation, RA patients showed significant increase in TAC and vitamin C level and significant decrease in MDA and 8 OHdG levels, plasma caspase 9 level was not significantly affected after vitamin C supplementation. Increased oxidative stress and decreased apoptosis may have an important role in the pathogenesis of RA. The administration of vitamin C supplementation may help to relieve oxidative stress and enhance the antioxidant defense in these patients.

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Section: Discussionsupporting

confidence: 66%

Evaluation of the effect of vitamin C on caspase 9 and oxidative stress in rheumatoid arthritis patients

Elshamy¹,

Gaafar²,

ElAshwah³

et al. 2018

Afr. J. Biochem. Res.

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“…Fibroblast‐like synoviocytes (FLS) could form the synovial intimal lining of diarthrodial joints, they also respond to pro‐inflammatory stimuli such as tumor necrosis factor (TNF)‐α and interleukin (IL)‐1 and exhibit features of inflammatory cells contributing to the pathogenesis of RA . Previous studies have confirmed that FLS play crucial roles in this process by producing cytokines that perpetuate autoimmune inflammation and proteases that contribute to cartilage destruction .…”

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confidence: 99%

NLRP6 facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid arthritis fibroblast‐like synoviocytes

Yang

Luo

2017

FEBS Letters

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In the present study, we investigated the role of nucleotide oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in rheumatoid arthritis (RA) and explored the underlying mechanism. We found that both mRNA and protein levels of NLRP6 are attenuated in synovial tissues and fibroblast-like synoviocytes (FLS) of RA patients compared to patients with osteoarthritis. We also observed that pro-inflammatory cytokine production is decreased and nuclear factor-kappa B activation is inhibited in NLRP6-overexpressing RA-FLS. Furthermore, we found that NLRP6 overexpression promotes transforming growth factor-b-activated kinase 1-binding protein 2/3 lysosome-dependent degradation, and we provide evidence showing that NLRP6 plays the role of providing the docking site to facilitate the interaction between transforming growth factor-b-activated kinase 1-binding protein 2/3 and tripartite motif 38 in RA-FLS.

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“…XIAP is an inhibitor of apoptosis protein that binds to the apoptotic promoter Caspase 9 and the effector Caspase 3 and 7 [29]. A previous study had shown that resistance to apoptosis in RA-FLS depends on the upregulation of XIAP [30]. IHC for XIAP, Bcl-2, and Bax of ankle and knee joins synovial tissues indicated that the expressions of Bcl-2 and XIAP were decreased and the expression of Bax was increased, resulting in a declined Bcl-2/Bax ratio in CIA rats following JWFSN administration.…”

Section: Discussionmentioning

confidence: 99%

Effect of Jiawei Fengshining on Synovial Cell Apoptosis and TGF-β1/Smad Signaling Pathway in Rats with Rheumatoid Arthritis

Dong

Gao

Ding

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Background/Aims. Jiawei Fengshining (JWFSN) is a new formula originated from Fengshining, a classic formula for the treatment of rheumatoid arthritis (RA). The mechanism of JWFSN in the treatment of RA is still unclear. The aim of this study was to evaluate the effect of JWFSN formula on the inflammatory mediator levels in the serum and the TGF-β1/Smad pathway in the synovium and to explore the underlying mechanisms of JWFSN formula to ameliorate synovial hyperplasia and apoptosis inhibition of synovium in rats with RA. Method. SPF female Wistar rats were randomly divided into 6 groups: the blank control group, the model control group, the positive drug group, and the low-, medium-, and high- dose JWFSN groups, with 8 rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory mediators, anti-inflammatory mediators, and rheumatoid factor (RF). The pathological condition and apoptosis of the synovial tissue were detected by hematoxylin and eosin (HE) and TUNEL staining, respectively. TGF-β1, p-Smad2, p-Smad3, and Smad7 protein expressions in synovial tissue were measured by western blot assay. In addition, human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A was treated with 20% JWFSN-containing serum to obtain in vitro data. Result. The administration of JWFSN was found to ameliorate synovial hyperplasia and promote apoptosis; increase the serum contents of anti-inflammatory mediators; reduce inflammatory mediators and RF contents; and inhibit the TGF-β1/Smad signaling pathway in CIA rats. In vitro JWFSN treatment increased the apoptosis of MH7A cells and decreased cell viability. Additionally, JWFSN treatment inhibited the TGF-β1/Smad signaling pathway in MH7A cells. Interestingly, kartogenin (TGF-β1/Smad pathway activator) treament reversed the effects of JWFSN treatment. Conclusion. JWFSN may ameliorate inflammatory factors’ abnormality, synovial hyperplasia, and apoptosis inhibition of synovium via the TGF-β1/Smad signaling pathway.

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Smac127 Has Proapoptotic and Anti-Inflammatory Effects on Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Cited by 6 publications

References 36 publications

Evaluation of the effect of vitamin C on caspase 9 and oxidative stress in rheumatoid arthritis patients

Evaluation of the effect of vitamin C on caspase 9 and oxidative stress in rheumatoid arthritis patients

NLRP6 facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid arthritis fibroblast‐like synoviocytes

Effect of Jiawei Fengshining on Synovial Cell Apoptosis and TGF-β1/Smad Signaling Pathway in Rats with Rheumatoid Arthritis

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