TNFR1 and TNFR2 differentially mediate TNF-α-induced inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes

2017 ◽  
Vol 41 (4) ◽  
pp. 415-422 ◽  
Author(s):  
Hongfeng Zhang ◽  
Weiguo Xiao
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Tnf Α ◽  
Fibroblast Like Synoviocytes

scholarly journals Evaluation of TAK-242 (Resatorvid) Effects on Inflammatory Status of Fibroblast-like Synoviocytes in Rheumatoid Arthritis and Trauma Patients

2021 ◽  
Author(s):  
Jafar Karami ◽  
Elham Farhadi ◽  
Ali-Akbar Delbandi ◽  
Mehdi Shekarabi ◽  
Mohammad Naghi Tahmasebi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Trauma Patients ◽  
Mrna Levels ◽  
Control Groups ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Fibroblast Like Synoviocytes

Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis )RA( pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-β, IL-6, TNF-α, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikβα and pIkβα) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-β, IL-6, TNF-α, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikβα and pIkβα by western blot. The baseline expression of IL1-β, IL-6, TNF-α, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1β, IL-6, TNF-α, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkβα in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients.

scholarly journals SAT0007 BLOCKING HISTAMINE-RELEASING FACTOR/TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (HRF/TCTP) ATTENUATES AGGRESSIVENESS OF FIBROBLAST-LIKE SYNOVIOCYTES AND AMELIORATES COLLAGEN-INDUCED ARTHRITIS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 934.3-934
Author(s):  
M. Kim ◽  
Y. Choe ◽  
H. Lee ◽  
Y. H. Cheon ◽  
S. I. Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Serum Levels ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Translationally Controlled Tumor Protein ◽  
Biochemical Analyses ◽  
Fibroblast Like Synoviocytes

Background:Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses. Increased expression of HRF/TCTP occurs in joints of rheumatoid arthritis (RA) patients, but the role of HRF/TCTP in RA remains undefinedObjectives:In this study, we explored the pathogenic significance of HRF/TCTP and evaluated therapeutic effects of HRF/TCTP blockade in RA.Methods:HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine experimental phenotypes of RA. HRF/TCTP levels were measured in sera and joint fluids in patients with RA and compared to those with osteoarthritis, ankylosing spondylitis, Behcet disease, and healthy controls. HRF/TCTP expression was also assessed in synovium and fibroblast-like synoviocytes (FLS) obtained from RA or OA patients. Finally, we assessed effects of HRF/TCTP and dimerized HRF/TCTP binding peptide-2 (dTBP2), an inhibitor of HRF/TCTP, in RA-FLS and CIA mice.Results:Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice, and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels were higher in sera, synovial fluid, synovium, and FLS of patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with disease activity in RA. Tumor-like aggressiveness of RA-FLS was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice, and had no detrimental effect in a murine tuberculosis model.Conclusion:Our results indicate that HRF/TCTP represents a novel biomarker and therapeutic target for diagnosis and treatment of RA.References:N/AAcknowledgments :National Research Foundation of KoreaKorea Health Industry Development InstituteDisclosure of Interests:None declared

Carvacrol suppresses inflammatory responses in rheumatoid arthritis fibroblast‐like synoviocytes

2018 ◽  
Vol 120 (5) ◽  
pp. 8169-8176 ◽  
Author(s):  
Yu Li ◽  
Jian‐zhong Xu ◽  
Chen‐xi Gu ◽  
Guan‐lei Liu ◽  
Ke Tian
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Fibroblast Like Synoviocytes

scholarly journals LAIR-1 shedding from human fibroblast-like synoviocytes in rheumatoid arthritis following TNF-α stimulation

2018 ◽  
Vol 192 (2) ◽  
pp. 193-205 ◽  
Author(s):  
Y. Zhang ◽  
S. Wang ◽  
H. Dong ◽  
X. Yi ◽  
J. Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Fibroblast ◽  
Tnf Α ◽  
Fibroblast Like Synoviocytes

scholarly journals Structural insights into heme binding to IL-36α proinflammatory cytokine

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amelie Wißbrock ◽  
Nishit B. Goradia ◽  
Amit Kumar ◽  
Ajay Abisheck Paul George ◽  
Toni Kühl ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Investigation ◽  
Inflammatory Responses ◽  
Structural Features ◽  
Solution Nmr ◽  
Heme Binding ◽  
Structural Framework ◽  
Spectroscopic Analyses ◽  
Structural Insights ◽  
Fibroblast Like Synoviocytes

AbstractCytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins.

Atomic Force Microscopy Study of the Anti-inflammatory Effects of Triptolide on Rheumatoid Arthritis Fibroblast-like Synoviocytes

2017 ◽  
Vol 23 (5) ◽  
pp. 1002-1012 ◽  
Author(s):  
Zhanhui Su ◽  
Han Sun ◽  
Man Ao ◽  
Chunying Zhao
Keyword(s):  
Rheumatoid Arthritis ◽  
Atomic Force Microscopy ◽  
Inflammatory Responses ◽  
Bone Destruction ◽  
Microscopy Study ◽  
Primary Role ◽  
Force Microscopy ◽  
Atomic Force ◽  
Anti Inflammatory ◽  
Fibroblast Like Synoviocytes

AbstractHigh-resolution atomic force microscopy (AFM) was used for the in situ evaluation of the anti-inflammatory effects of triptolide on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to understand the anti-RA effects of triptolide, based on the morphological and biophysical changes observed in RA-FLS. RA-FLS have been reported to play a primary role in inflammatory bone destruction during the development of RA and thus are regarded as an important target for RA treatment. Triptolide pretreatment significantly inhibited tumor necrosis factor-α-induced expression of the interleukin (IL)-1β, IL-6, and IL-8 genes in MH7A cells. Using AFM, we showed that triptolide-induced morphological damage in MH7A cells by inducing significant ultrastructure changes in the membrane, which were closely related to triptolide-induced apoptosis in MH7A cells. Using force measurements determined with AFM, triptolide was shown to increase the stiffness of MH7A cells. These findings not only revealed the strong anti-inflammatory effects of triptolide on RA-FLS, highlighting triptolide as a potential anti-RA agent, but also revealed the possible use of AFM for studying anti-inflammatory responses in RA-FLS, which we expect to be developed into a potential tool for anti-RA drug studies in RA-FLS.

scholarly journals Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Zhijun Jiao ◽  
Wenhong Wang ◽  
Jie Ma ◽  
Shengjun Wang ◽  
Zhaoliang Su ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Notch Signaling ◽  
Target Gene ◽  
Cytokine Production ◽  
Notch Pathway ◽  
Mrna Levels ◽  
Secretase Inhibitor ◽  
Tnf Α ◽  
Functional Involvement ◽  
Fibroblast Like Synoviocytes

It has been reported that Notch family proteins are expressed in synovium tissue and involved in the proliferation of synoviocyte from rheumatoid arthritis (RA). The aim of this paper was to investigate whether Notch signaling mediated TNF-α-induced cytokine production of cultured fibroblast-like synoviocytes (FLSs) from RA. Exposure of RA FLSs to TNF-α(10 ng/ml) led to increase of Hes-1, a target gene of Notch signaling, and a marked upregulation of Notch 2, Delta-like 1, and Delta-like 3 mRNA levels. Blockage of Notch signaling by aγ-secretase inhibitor (DAPT) inhibited IL-6 secretion of RA FLSs in response to TNF-αwhile treatment with recombinant fusion protein of Notch ligand Delta-like 1 promoted such response. TNF-αstimulation also induced IL-6 secretion in OA FLSs; however, the Hes-1 level remained unaffected. Our data confirm the functional involvement of Notch pathway in the pathophysiology of RA FLSs which may provide a new target for RA therapy.

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