A20 suppresses inflammatory responses and bone destruction in human fibroblast‐like synoviocytes and in mice with collagen‐induced arthritis

Hah, Young‐Sool; Lee, Young‐Rae; Jun, Jin-Su; Lim, H.-H.; Kim, Hyun-Ok; Jeong, Yujin; Hur, Gang Min; Lee, Sang Yong; Chung, Myoung Ja; Park, Jin-Woo; S, Lee; Park, Byung‐Hyun

doi:10.1002/art.27545

Cited by 71 publications

(52 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Induction and assessment of CIA CIA was induced as previously described [16] . Bovine Type II collagen (CII; Sigma; St Louis, MO, USA) was dissolved to a concentration of 2 mg/mL in 0.01 mol/L acetic acid at 4 °C, with constant overnight mixing.…”

Section: Animalsmentioning

confidence: 99%

“…In response to a variety of stimuli, including proinflammatory cytokines such as TNF-α, IL-6 and IL-1β as well as LPS, inhibitory IκB is degraded by the ubiquitin-proteasome pathway, leading to nuclear translocation of NF-κB and transcription of many genes encoding proinflammatory proteins [12,13] . NF-κB is highly activated in the synovial tissue of RA patients [14,15] and in mice with collagen-induced arthritis (CIA) [16] . Electromobility shift assays demonstrate that NF-κB binding is significantly higher in RA synovium compared with osteoarthritis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis

Jin¹,

Yan

Wang

et al. 2016

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Hyperoside is a flavonol glycoside mainly found in plants of the genera Hypericum and Crataegus, which has shown anti-oxidant, anti-cancer and anti-inflammatory activities. In this study, we investigated the effects of hyperoside on human rheumatoid fibroblastlike synoviocytes (FLSs) in vitro and on mouse collagen-induced arthritis (CIA) in vivo. Methods: FLSs were isolated from primary synovial tissues obtained from rheumatoid arthritis (RA) patients and exposed to LPS (1 µg/mL). Cell viability and proliferation were measured with MTT and BrdU assay. Cell migration was assessed using wound-healing assay and Transwell assay. DNA binding of NF-κB was measured using a TransAM-NFkappaB kit. The localization of p65 subunit was detected with immunocytochemistry. CIA was induced in mice by primary immunization with Bovine Type II collagen (CII) emulsified in CFA, followed by a booster injection 3 weeks later. The arthritic mice were treated with hyperoside (25, 50 mg·kg -1 ·d -1, ip) for 3 weeks, and the joint tissues were harvested for histological analysis. Results: Hyperoside (10, 50, 100 µmol/L) dose-dependently inhibited LPS-induced proliferation and migration of human RA FLSs in vitro. Furthermore, hyperoside decreased LPS-stimulated production of TNF-α, IL-6, IL-1 and MMP-9 in the cells. Moreover, hyperoside inhibited LPS-induced phosphorylation of p65 and IκBα, and suppressed LPS-induced nuclear translocation of p65 and DNA biding of NF-κB in the cells. Three-week administration of hyperoside significantly decreased the clinical scores, and alleviated synovial hyperplasia, inflammatory cell infiltration and cartilage damage in mice with CIA. Conclusion: Hyperoside inhibits LPS-induced proliferation, migration and inflammatory responses in human RA FLSs in vitro by suppressing activation of the NF-κB signaling pathway, which contributes to the therapeutic effects observed in mice with CIA.

show abstract

Section: Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis

Jin¹,

Yan

Wang

et al. 2016

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…RA is a chronic destructive disease of the joints that is characterized by hyperplastic synovitis due to resistance to apoptosis, infiltration of inflammatory cells into synovial tissue and joint destruction (21). As one of the NF-κB target genes, TNFAIP3 has been well established for its negative-feedback mechanism to block NF-κB activation through its ubiquitin-editing function in response to various inflammatory signaling, including TNF, IL-1β and lipopolysaccharides (12,13,22,23).…”

Section: Discussionmentioning

confidence: 99%

Altered TNFAIP3 mRNA expression in peripheral blood mononuclear cells from patients with rheumatoid arthritis

et al. 2015

View full text Add to dashboard Cite

Abstract. The tumor necrosis factor α-induced protein-3 (TNFAIP3) gene functions in negative immunoregulation and its single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA) disease. However, its expression level in immune cells from RA patients remains unclear. The aim of the present study was to investigate whether the expression of TNFAIP3 is changed in patients with RA. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine TNFAIP3 mRNA expression in peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls. TNFAIP3 expression was decreased in RA patients compared with the healthy controls. The expression level of the TNFAIP3 gene negatively correlated with the RA score, anti-cyclic citrullinated peptide (CCP) antibody levels and C-reactive protein levels. Furthermore, RA patients with positive results of anti-CCP antibodies had a lower expression of TNFAIP3 than those without anti-CCP antibodies. In conclusion, the present results suggest that the insufficient expression of the TNFAIP3 gene in PBMCs may correlate with the diagnosis of RA. IntroductionRheumatoid arthritis (RA) is a common chronic inflammatory disease that predominantly affects the small joints of the hands and feet (1). The propagation of inflammation is characterized by migration of mononuclear cells into the local inflammatory sites, leading to the hyperplasia of fibroblast-like synoviocytes (FLSs) primarily due to resistance to apoptosis and damage to cartilage and bone (2). The chronic inflammation is attributed to breakdown of immune homostasis, which results in activation of immune cells and elevation of pro-inflammatory cytokines (3). The immune activation leads to deposition of immune complexes and mononuclear cell infiltration into susceptible organs, while the pro-inflammatory cytokines are responsible for maintenance of the immune activation (4). The major mediators of chronic inflammation in RA include tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-8 and prostaglandin E2 (5). Induction of pro-inflammatory mediators requires activation of the nuclear factor (NF)-κB inducing kinase-or inhibitor of NF-κB (IκB) kinase-mediated NF-κB signal transduction pathways (6,7). The transcription factor NF-κB has been well recognized as a key regulator of inflammation in RA (8-10).TNF-α-induced protein-3 (TNFAIP3) is an important negative immunoregulatory gene. TNFAIP3 is a dual ubiquitin-editing enzyme, whose expression is induced by a large number of stimuli in a wide variety of cells (11). Evidence from animal models indicates that TNFAIP3 is a plausible candidate gene in RA susceptibility (11). In TNFAIP3 knockout mice, its deficiency leads to death shortly following birth by severe inflammation and tissue damage in multiple organs (12,13). In immune cells, overexpression of TNFAIP3 can terminate NF-κB signaling transduced from TNF receptors, toll-like receptors, nucleotide-binding oligomerization domain containing 2 receptors or T ...

show abstract

“…However, the overexpression of A20 may be attenuated and has a protective effect in the inflammatory response in mouse models of allergic asthma and rheumatoid arthritis and other inflammatory pathological autoimmune diseases. These results suggest that A20 is an ideal target molecule for slowing the inflammatory response [36-37]. …”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of MiR-136-5p Targeting NF-κB/A20 in the IL-17-Mediated Inflammatory Response after Spinal Cord Injury

He¹,

Zhao²,

Peng³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The pathophysiology of spinal cord injury (SCI) results in serious damage to the human body via an increase in the secondary biological processes imposed by activated astrocytes. Abnormal expression of microRNAs after SCI has become a potential research focus. However, the underlying mechanisms are poorly understood. Methods: SCI models were established in rats using Allen’s method, and the BBB scoring method was employed to assess locomotor function. Lentivirus was used to infect rat astrocytes and SCI rats. Real-time PCR and antibody chip were used to measure gene expression and cytokine secretion. Western blot analysis was employed to detect protein expression. HE staining was used to assess the histological changes in SCI. The immunohistochemical staining of A20 and p-NF-κB in SCI was also analyzed. Results: The in vitro experiment showed that miR-136-5p up-regulated the expression of p-NF-κB by down-regulating the expression of A20 so that astrocytes produced inflammatory factors and chemokines. The in vivo experiment indicated that overexpressed miR-136-5p promoted the production of inflammatory factors, chemokines and p-NF-κB in SCI rats, whereas it inhibited the expression of A20 protein and increased inflammatory cell infiltration and injuries in the spinal cord. Conclusion: The current findings indicate that silencing miR-136-5p effectively decreased inflammatory factors and chemokines and protected the spinal cord via NF-κB/A20 signaling in vivo and in vitro. In contrast, overexpression of miR-136-5p had the opposite effect.

show abstract

A20 suppresses inflammatory responses and bone destruction in human fibroblast‐like synoviocytes and in mice with collagen‐induced arthritis

Cited by 71 publications

References 32 publications

Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis

Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis

Altered TNFAIP3 mRNA expression in peripheral blood mononuclear cells from patients with rheumatoid arthritis

Molecular Mechanism of MiR-136-5p Targeting NF-κB/A20 in the IL-17-Mediated Inflammatory Response after Spinal Cord Injury

Contact Info

Product

Resources

About