scholarly journals Dishevelled2 promotes apoptosis and inhibits inflammatory cytokine secretion in rheumatoid arthritis fibroblast-like synoviocytes through crosstalk with the NF-κB pathway

Oncotarget ◽  
2017 ◽  
Vol 8 (8) ◽  
pp. 12649-12663 ◽  
Author(s):  
Xing Zhen Liu ◽  
Jie Fan ◽  
Ke Qi ◽  
Shu Peng Liu ◽  
Wei Dong Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokine ◽  
Cytokine Secretion ◽  
Fibroblast Like Synoviocytes

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.

Over expression of IL-32 in rheumatoid arthritis modulates NF-κB activity

2019 ◽  
Vol 7 (1) ◽  
pp. 24-36
Author(s):  
Sergio Ayala ◽  
Peter G. Thury
Keyword(s):  
Rheumatoid Arthritis ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Inflammatory Cytokine ◽  
Cytokine Secretion ◽  
Nuclear Factor ◽  
Over Expression ◽  
Cellular Processes ◽  
Control Subjects ◽  
Promising Target

IL-32 is pro-inflammatory cytokine characterized by the induction of nuclear factor NF-κB activation and an important role in key cellular processes related to inflammation. We investigated whether the IL-32 expression may be involved in the mehanistic of rheumatoid arthritis through modulates the activity of NF-κB. We report that the concentrations of IL-32 are higher in the serums of RA patients than of control subjects. Results show that IL-32 induces the production of the proinflammatory cytokines IL-1-beta, IL-6, and increased NF-κB activation. We concluded that these data show that IL-32 is constitutively produced by RA synoviocytes, induces proinflammatory cytokine secretion, and activation NF-κB. IL-32 thereby may constitute a promising target to treat RA.

scholarly journals Effects of inflammatory cytokine IL-27 on the activation of fibroblast-like synoviocytes in rheumatoid arthritis

2010 ◽  
Vol 12 (4) ◽  
pp. R129 ◽  
Author(s):  
Chun K Wong ◽  
Da P Chen ◽  
Lai S Tam ◽  
Edmund K Li ◽  
Yi B Yin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokine ◽  
Fibroblast Like Synoviocytes

Lymphotoxin α stimulates proliferation and pro-inflammatory cytokine secretion of rheumatoid arthritis synovial fibroblasts

Cytokine ◽  
2011 ◽  
Vol 53 (2) ◽  
pp. 207-214 ◽  
Author(s):  
Flavia Calmon-Hamaty ◽  
Bernard Combe ◽  
Michael Hahne ◽  
Jacques Morel
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokine ◽  
Synovial Fibroblasts ◽  
Cytokine Secretion ◽  
Lymphotoxin Α

scholarly journals Parallel comparison of fibroblast-like synoviocytes from the surgically removed hyperplastic synovial tissues of rheumatoid arthritis and osteoarthritis patients

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei Huang ◽  
Linlin Zhang ◽  
Chao Cheng ◽  
Wenshan Shan ◽  
Ruixiang Ma ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokine ◽  
Cellular Functions ◽  
Cell Surface Antigens ◽  
Necrosis Factor Alpha ◽  
Inflammatory Status ◽  
Cytokine Tumor Necrosis Factor ◽  
Anti Inflammatory ◽  
Synovial Tissues ◽  
Fibroblast Like Synoviocytes

Abstract Background Fibroblast-like synoviocytes (FLS) are essential cellular components in inflammatory joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Despite the growing use of FLS isolated from OA and RA patients, a detailed functional and parallel comparison of FLS from these two types of arthritis has not been performed. Methods In the present study, FLS were isolated from surgically removed synovial tissues from twenty-two patients with OA and RA to evaluate their basic cellular functions. Results Pure populations of FLS were isolated by a sorting strategy based on stringent marker expression (CD45−CD31−CD146−CD235a−CD90+PDPN+). OA FLS and RA FLS at the same passage (P2-P4) exhibited uniform fibroblast morphology. OA FLS and RA FLS expressed a similar profile of cell surface antigens, including the fibroblast markers VCAM1 and ICAM1. RA FLS showed a more sensitive inflammatory status than OA FLS with regard to proliferation, migration, apoptosis, inflammatory gene expression and pro-inflammatory cytokine secretion. In addition, the responses of OA FLS and RA FLS to both the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the anti-inflammatory drug methotrexate (MTX) were also evaluated here. Conclusion The parallel comparison of OA FLS and RA FLS lays a foundation in preparation for when FLS are considered a potential therapeutic anti-inflammatory target for OA and RA.

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