Chemical inhibition of HSP90 inhibits TNF‐α mediated proliferation and induces apoptosis in human rheumatoid arthritis fibroblast‐like synoviocytes

2018 ◽  
Vol 120 (2) ◽  
pp. 2547-2553 ◽  
Author(s):  
Bin Yang ◽  
Xiangru Liu ◽  
Yongqian Liang ◽  
Yue Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Rheumatoid Arthritis ◽  
Tnf Α ◽  
Chemical Inhibition ◽  
Fibroblast Like Synoviocytes

scholarly journals Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 587
Author(s):  
Fu-Tzu Pai ◽  
Cheng-You Lu ◽  
Chia-Hsin Lin ◽  
John Wang ◽  
Ming-Cheng Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Suppressor Cells ◽  
Clinical Severity ◽  
Histopathological Analysis ◽  
Human Rheumatoid Arthritis ◽  
Psoralea Corylifolia ◽  
Collagen Induced Arthritis ◽  
Tnf Α ◽  
Synovial Tissues ◽  
Orthopedic Diseases

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

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.

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
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