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 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

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 MiR-498 suppresses proliferation and inflammation in fibroblast-like synoviocytes in rheumatoid arthritis via targeting JAK1

2021 ◽  
Vol 18 (10) ◽  
pp. 2011-2017
Author(s):  
Lan Chai ◽  
Xian Zhen Zhang ◽  
Hai fang Ma ◽  
Fang Yuan
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Cycle ◽  
Polymerase Chain Reaction ◽  
Therapeutic Target ◽  
Cell Apoptosis ◽  
Inflammatory Responses ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Synovial Tissues ◽  
Fibroblast Like Synoviocytes

Purpose: To investigate the effect of microRNA 498 (miR-498) on proliferation and inflammation of rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLSs) in rheumatoid arthritis (RA). Methods: MiR-498 level was evaluated in both RA synovial tissues and RA-FLSs using real-time polymerase chain reaction (PCR). MicroRNA-498 overexpression or knockdown was performed in RAFLSs. Proliferation, apoptosis, cell cycle and inflammation induced by miR-498 mimics or inhibitor were used to explore the function of miR-498 in RA. Results: Expression level of miR-498 was downregulated in both RA synovial tissues and RA- FLSs. MicroRNA-498 mimics decreased proliferation and arrested cell cycle, whereas miR-498 inhibitor caused the opposite effects in RA-FLSs. In addition, miR-498 mimics suppressed inflammation and promoted cell apoptosis, while miR-498 inhibitor promoted inflammation and inhibited cell apoptosis in RA-FLSs. Furthermore, the effect of miR-498 on the proliferation, inflammation and apoptosis of RAFLSs was mediated by its ability to target and downregulate JAK1. Conclusion: These results indicate that miR-498 inhibits the proliferation and inflammatory responses of RA-FLSs by targeting JAK1, thus revealing a new therapeutic target for RA treatment.

scholarly journals MicroRNA-146a suppresses rheumatoid arthritis fibroblast-like synoviocytes proliferation and inflammatory responses by inhibiting the TLR4/NF-kB signaling

Oncotarget ◽  
2018 ◽  
Vol 9 (35) ◽  
pp. 23944-23959 ◽  
Author(s):  
Wei Liu ◽  
Yuan-Hao Wu ◽  
Lei Zhang ◽  
Bin Xue ◽  
Yi Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Fibroblast Like Synoviocytes

AB0110 ADIPONECTIN INDUCES PRO-INFLAMMATORY CHEMOKINE AND CYTOKINE PRODUCTION BY PERIPHERAL BLOOD MONONUCLEAR CELLS AND FIBROBLAST-LIKE SYNOVIOCYTES FROM NON-INFLAMED SUBJECTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1355-1356
Author(s):  
Y. Zhang ◽  
J. Aldridge ◽  
G. K. Vasileiadis ◽  
A. C. Lundell ◽  
A. Rudin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Multiplex Assay ◽  
Human Pbmcs ◽  
Peripheral Blood Mononuclear ◽  
Preclinical Phase ◽  
Blood Mononuclear Cells ◽  
Fibroblast Like Synoviocytes

Background:Adiponectin is a cytokine mainly secreted by the adipose tissue1, whose circulating levels are paradoxically low in subjects with obesity and associate with a beneficial metabolic profile2., Recent studies have shown that adiponectin levels are elevated in both serum and synovial fluid collected from patients with rheumatoid arthritis (RA)3,4. Moreover, adiponectin is able to induce the production of interleukin (IL)-6, tumor necrosis factor (TNF), CXCL1 and CXCL8 by lymphocytes from healthy subjects5, and of IL-6 and CXCL8 by fibroblast-like synoviocytes (FLS) from patients with RA6. However, it is not clear if adiponectin is able to initiate the inflammatory processes associated with the preclinical phase of RA.Objectives:We aim to determine if adiponectin is able to induce inflammatory responses in peripheral blood mononuclear cells (PBMCs) and FLS from non-inflamed subjects.Methods:Human PBMCs were collected from healthy donors, whereas non-inflamed FLS from non-arthritic patients who underwent diagnostic arthroscopy due to previous trauma. PBMCs (1× 105cells/well in 96-well plate) and FLS (5000 cells/well in 96-well plate) were stimulated using 5 μg/ml recombinant human total adiponectin protein, and the supernatants were collected 48 hours after stimulation. Phytohemagglutinin (PHA) and TNF were used as positive controls to activate PBMCs and FLS, respectively. Using multiplex assay and ELISA, we screened the production of 13 chemokines and 12 cytokines from healthy human PBMCs and non-inflamed FLS.Results:Adiponectin was able to stimulate a distinct profile of chemokines and cytokines in PBMCs and FLS. In both healthy PBMCs and non-inflamed FLS adiponectin induced the production of CXCL1, CXCL5, CXCL8, CCL2 and IL-6. Moreover, CCL3, CCL20, CCL4, CCL17, TNF, IL-10 and GM-CSF were induced by adiponectin only in healthy PBMCs, whereas CXCL10, CCL5 and CCL11 only in non-inflamed FLS (Fig. 1 and 2).Figure 1.Adiponectin induces the production of various chemokines from PBMCs (A) and FLS (B). CXCL8 (#) was measured using ELISA, and other chemokines were measured using multiplex assay. The fold change of CXCL1 in FLS (†) was not calculated because its level before stimulation was undetectable.Conclusion:We here report that adiponectin has pro-inflammatory properties as it induced chemokine and cytokine production from human healthy PBMCs and non-inflamed FLS. As adiponectin is able to induce pro-inflammatory responses from non-inflamed cells, we suggest that this adipokine might be implicated in the preclinical phase of RA pathogenesis.References:[1]Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013;2013:139239.[2]Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 2014;105:141-50.[3]Otero M, Lago R, Gomez R, et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65:1198-201.[4]Schaffler A, Ehling A, Neumann E, et al. Adipocytokines in synovial fluid. JAMA 2003;290:1709-10.[5]Frommer KW, Zimmermann B, Meier FM, et al. Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis. Arthritis Rheum 2010;62:2886-99.[6]Kitahara K, Kusunoki N, Kakiuchi T, Suguro T, Kawai S. Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts. Biochem Biophys Res Commun 2009;378:218-23.Figure 2.Adiponectin induces the production of IL-6 PBMCs (A) FLS (B) measured using ELISA.Disclosure of Interests:Yuan Zhang: None declared, Jonathan Aldridge: None declared, Georgios K. Vasileiadis: None declared, Anna-Carin Lundell: None declared, Anna Rudin Consultant of: Astra/Zeneca, Cristina Maglio: None declared

scholarly journals TRIM32 promotes inflammatory responses in rheumatoid arthritis fibroblast‐like synoviocytes

2020 ◽  
Vol 91 (6) ◽  
Author(s):  
Tian Liang ◽  
Min Song ◽  
Kewu Xu ◽  
Chenglong Guo ◽  
Hongbin Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Fibroblast Like Synoviocytes

Sprouty2 suppresses the inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes through regulating the Raf/ERK and PTEN/AKT signals

2015 ◽  
Vol 67 (2) ◽  
pp. 532-539 ◽  
Author(s):  
Wei Zhang ◽  
Zhiyan Du ◽  
Jingying Zhu ◽  
Jiyun Yu ◽  
Yuanji Xu
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
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.

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