Celastrol inhibits interleukin-17A-stimulated rheumatoid fibroblast-like synoviocyte migration and invasion through suppression of NF-κB-mediated matrix metalloproteinase-9 expression

Li, Guoqing; Zhang, Yu; Liu, Dan; Qian, Yayun; Zhang, Hua; Guo, Shiyu; Sunagawa, Makoto; Hisamitsu, Tadashi; Liu, Yanqing

doi:10.1016/j.intimp.2012.08.016

Cited by 29 publications

(21 citation statements)

References 41 publications

(50 reference statements)

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“…Previously, we demonstrated that celastrol inhibited IL-17A-induced migration and invasion by suppression of NF-κB mediated MMP-9 expression and activity in human RA-FLSs [22]. LPS can stimulate FLS to secrete MMPs, and this induction is regulated at the transcriptional and translational levels [10].…”

Section: Discussionmentioning

confidence: 96%

“…1A) isolated from Celastrus scandens was obtained from Calbiochem (La Jolla, CA, USA). The powder was dissolved in dimethyl sulfoxide (DMSO) and stored as aliquots (20 mM) at −20°C until used, following the method described previously [22]. Celastrol was dissolved in 10% DMSO, and vehicle (distilled water containing 10% DMSO) was used as a control.…”

Section: Methodsmentioning

confidence: 99%

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Celastrol Inhibits Lipopolysaccharide-Stimulated Rheumatoid Fibroblast-Like Synoviocyte Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Liú

Zhang

et al. 2013

PLoS ONE

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Invasion of fibroblast-like synoviocytes (FLSs) is critical in the pathogenesis of rheumatoid arthritis (RA). The metalloproteinases (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasive activity of celastrol on LPS-stimulated human RA-FLSs, and to elucidate the mechanism involved. We investigated the effect of celastrol on LPS-induced FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that celastrol suppressed LPS-stimulated FLS migration and invasion by inhibiting MMP-9 expression and activity. Furthermore, our results revealed that celastrol inhibited the transcriptional activity of MMP-9 by suppressing the binding activity of NF-κB in the MMP-9 promoter, and suppressed the TLR4/MyD88/NF-κB pathway. Administration of celastrol (0.5 mg/kg and 1 mg/kg, intraperitoneally) daily for 3 weeks in a collagen-induced arthritis rat model markedly alleviated the clinical signs, synovial hyperplasia and inflammatory cell infiltration of joints. In conclusion, celastrol might inhibit FLS migration and invasion induced by LPS by suppressing TLR4/NF-κB-mediated MMP-9 expression, providing a theoretical foundation for the clinical treatment of RA with celastrol.

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Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Celastrol Inhibits Lipopolysaccharide-Stimulated Rheumatoid Fibroblast-Like Synoviocyte Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Liú

Zhang

et al. 2013

PLoS ONE

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“…It inhibits MMP-9 transcription through the suppression of the binding activity of NF-kB in the promoter and the TLR4/MyD88/NF-kB pathway signaling (42). Previously, these authors have also reported that celastrol inhibits IL-17-induced migration and invasion of human RA-FLS by suppression of NF-kB-mediated MMP-9 expression and activity (43). In addition, under hypoxic conditions mimicking the synovial hypoxia of arthritic joints, it has been found that celastrol decreases hypoxia-induced FLS invasion by inhibiting HIF-1α-mediated CXCR4 transcription (44).…”

Section: Anti-inflammatory Properties Of Celastrolmentioning

confidence: 94%

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

2017

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The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness.

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“…The underlying mechanism for this effect was the ability of celastrol to induce heme oxygenase-1 (HO-1), inhibit the effect of interferon gamma (IFNγ)-induced monocyte adhesion, and down-regulate ICAM-1 [166]. A similar effect on inflammatory cytokine expression in human THP-1 and T cells was noted in other studies [170–172]. Toxicological analysis performed on zebra fish have shown that 1 μM celastrol is toxic for this animal model as a high rate of mortality was observed 48 hours after exposure.…”

Section: Natural Anti-inflammatory Compounds To Modulate Inflammatmentioning

confidence: 73%

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

Yanez

Blanchette

Jabbarzadeh

2018

CPD

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Tissue engineering offers a promising strategy to restore injuries resulting from trauma, infection, tumor resection, or other diseases. In spite of significant progress, the field faces a significant bottleneck; the critical need to understand and exploit the interdependencies of tissue healing, angiogenesis, and inflammation. Inherently, the balance of these interacting processes is affected by a number of injury site conditions that represent a departure from physiological environment, including reduced pH, increased concentration of free radicals, hypoglycemia, and hypoxia. Efforts to harness the potential of immune response as a therapeutic strategy to promote tissue repair have led to the identification of natural compounds with significant anti-inflammatory properties. This article provides a concise review of the body’s inflammatory response to biomaterials and describes the role of oxygen as a physiological cue in this process. We proceed to highlight the potential of natural compounds to mediate inflammatory response and improve host-graft integration. Herein, we discuss the use of natural compounds to map signaling molecules and checkpoints that regulate the cross-linkage of immune response and skeletal repair.

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Celastrol inhibits interleukin-17A-stimulated rheumatoid fibroblast-like synoviocyte migration and invasion through suppression of NF-κB-mediated matrix metalloproteinase-9 expression

Cited by 29 publications

References 41 publications

Celastrol Inhibits Lipopolysaccharide-Stimulated Rheumatoid Fibroblast-Like Synoviocyte Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Celastrol Inhibits Lipopolysaccharide-Stimulated Rheumatoid Fibroblast-Like Synoviocyte Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

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