Bufalin, a Bioactive Component of the Chinese Medicine Chansu, Inhibits Inflammation and Invasion of Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Inflammation ◽  
2014 ◽  
Vol 37 (4) ◽  
pp. 1050-1058 ◽  
Author(s):  
Xiaofeng Rong ◽  
Weidong Ni ◽  
Yongguang Liu ◽  
Jun Wen ◽  
Chunyan Qian ◽  
...  
2021 ◽  
Vol 11 (9) ◽  
pp. 1744-1751
Author(s):  
Deqian Meng ◽  
Wenyou Pan ◽  
Ju Li

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.


PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0181003 ◽  
Author(s):  
Wenwen Wang ◽  
Jiahuan Liu ◽  
Binzhou Yang ◽  
Zhongshuang Ma ◽  
Guiping Liu ◽  
...  

2020 ◽  
Author(s):  
Camilla Machado ◽  
Adriana Kakehasi ◽  
Felipe Dias ◽  
Gustavo Resende ◽  
Patrícia Oliveira ◽  
...  

Abstract BackgroundFibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to compare ultrastructural characteristics and functional responses by human and mouse FLS. The objective of this study is to compare ultrastructural characteristics, IL-6 and MMP-3 production, and the activation of intracellular pathways in FLS from patients with RA (RA-FLS) and mice with collagen-induced arthritis (CIA-FLS). The objective of the study was to compare ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with Rheumatoid Arthritis (RA) and from mice with collagen-induced arthritis.MethodsFLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with collagen-induced arthritis (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor - alpha (TNF-α) and IL-1β.ResultsRA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs.ConclusionThere were differences between RA-FLSs and CIA-FLSs in their ultrastructural morphologies and functional responses. The differences shown in our study indicate that the adoption of an RA-FLS human model is a better alternative than the CIA-FLS animal model for in vitro studies of RA etiopathogenesis and new therapeutic targets.


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