Triptolide promotes the apoptosis and attenuates the inflammation of fibroblast‐like synoviocytes in rheumatoid arthritis by down‐regulating lncRNA ENST00000619282

2021 ◽  
Author(s):  
Jianting Wen ◽  
Jian Liu ◽  
Xin Wang ◽  
Jie Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Fibroblast Like Synoviocytes

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Inflammatory Processes ◽  
Related Proteins ◽  
Local Stimulation ◽  
Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

Circ_AFF2 facilitates proliferation and inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis via the miR-375/TAB2 axis

2021 ◽  
Vol 119 ◽  
pp. 104617
Author(s):  
Liqiang Zhi ◽  
Jingqi Liang ◽  
Wei Huang ◽  
Jianbing Ma ◽  
Zhong Qing ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
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

MicroRNA-16-5p Promoted Fibroblast-Like Synoviocyte Proliferation and Suppressed Apoptosis via Targeting Suppressor of Cytokine Signaling 6 (SOCS6) in Human Rheumatoid Arthritis

2021 ◽  
Vol 11 (9) ◽  
pp. 1744-1751
Author(s):  
Deqian Meng ◽  
Wenyou Pan ◽  
Ju Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Cytokine Signaling ◽  
Human Rheumatoid Arthritis ◽  
Reporter Assay ◽  
Functional Roles ◽  
Proliferation And Apoptosis ◽  
Fibroblast Like Synoviocytes

Accumulating evidence have indicated that MicroRNAs (miRNAs) are key regulators in human rheumatoid arthritis (RA). The aim of this study was to explore the functional roles of miR-16-5p in proliferation, inflammation, and apoptosis of fibroblast-like synoviocytes (FLS). The expression of miR-16-5p and SOCS6 in FLA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry, respectively. Luciferase reporter assay was used to verify the direct target of miR-16-5p. Western blot analysis was performed to analysis the levels of SOCS6, Bcl-2, Bax and cleaved caspase 3. miR-16-5p expression was significantly upregulated while SOCS6 level was decreased in RA-FLS compared with normal FLS. In addition, luciferase reporter assay confirmed that SOCS6 was the target of miR-16-5p. Silencing of miR-16-5p inhibited cell proliferation, releases of TNF-α, IL-1β, IL-6 and IL-8, and induced the apoptosis. The effects of miR-16-5p silencing on RA-FLS were reversed by downregulation of SOCS6. In summary, knockdown of miR-16-5p could suppress cell proliferation and accelerate the apoptosis of RA-FLS through targeting SOCS6, which may provide a potential therapeutic target for patients with RA.

Cationic Amino Acid Transporter-1 (CAT-1) Promotes Fibroblast-Like Synoviocytes Proliferation and Cytokine Secretion by Taking Up L-Arginine in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Ying Lu ◽  
Chongbo Hao ◽  
Shanshan Yu ◽  
Zuan Ma ◽  
Xuelian Fu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Amino Acid ◽  
Synovial Fluid ◽  
Culture Conditions ◽  
Cytokine Secretion ◽  
Cationic Amino Acid Transporter ◽  
Cationic Amino Acid ◽  
The Relationship ◽  
Fibroblast Like Synoviocytes

Abstract Background: Abnormal proliferation of fibroblast-like synoviocytes (FLSs) in the synovial lining layer is the primary cause of synovial hyperplasia and joint destruction in rheumatoid arthritis (RA). Currently, the relationship between metabolic abnormalities and FLS proliferation is a new focus of investigation. However, little is known regarding the relationship between amino acid metabolism and RA. Methods: The concentrations of amino acids and cytokines in the synovial fluid of RA (n=9) and osteoarthritis (OA,n=9) were detected by LC-MS/MS and CBA assay, respectively. The mRNA and protein expression of CAT-1 were determined in FLSs isolated from RA and OA patients by real-time PCR and western blotting. MTT assay, cell cycle, apoptosis, invasion and cytokine secretion were determined in FLSs knocked down of CAT-1 using siRNA or treated with D-arginine under normoxic and hypoxic culture conditions. A mouse collagen-induced arthritis (CIA) model was applied to test the therapeutic potential of blocking the uptake of L-arginine in vivo.Results: L-arginine was upregulated in the synovial fluid of RA patients and was positively correlated with elevation of the cytokines IL-1β, IL-6 and IL-8. Further examination demonstrated that cationic amino acid transporter-1 (CAT-1) was the primary transporter for L-arginine and was overexpressed on RA FLSs compared to OA FLSs. Moreover, knockdown of CAT-1 using siRNA or inhibition of L-arginine uptake using D-arginine significantly suppressed L-arginine metabolism, cell proliferation, migration and cytokine secretion in RA FLSs under normoxic and hypoxic culture conditions in vitro but increased cell apoptosis in a dose-dependent manner. Meanwhile, in vivo assays revealed that an L-arginine-free diet or blocking the uptake of L-arginine using D-arginine suppressed arthritis progression in CIA mice. Conclusion: CAT-1 is upregulated and promotes FLS proliferation by taking up L-arginine, thereby promoting RA progression.

THU0078 EXPRESSION PROFILE ANALYSIS OF LONG NONCODING RNAS INDUCED BY IL-1ß IN RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIOCYTES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 251.1-251
Author(s):  
J. M. Kim ◽  
H. J. Kang ◽  
S. J. Jung ◽  
B. W. Song ◽  
H. J. Jeong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Expression Profile ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Aberrant Expression ◽  
Iκb Kinase ◽  
Ngs Data ◽  
Fibroblast Like Synoviocytes

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared

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