Endothelin-1 Production by Human Synoviocytes

Author(s):  
Hiroshi Yoshida ◽  
Yuji Imafuku ◽  
Morihiro Ohhara ◽  
Masayuki Miyata ◽  
Reji Kasukawa ◽  
...  

Immunoreactive (ir)-endothelin (ET)-l concentrations in serum samples and synovial fluids from patients with rheumatoid arthritis were higher than concentrations in sera obtained from healthy volunteers. No significant difference in ir-ET-1 concentrations in synovial fluid was observed between rheumatoid arthritis patients and osteoarthritis patients. Cultured fluids of synovial cells collected from synovial tissues and leucocytes from synovial fluids of rheumatoid arthritis patients were studied to determine the origin of ir-ET-1 in synovial fluids. Ir-ET-1 was detected in the cultured fluids of synovial macrophage-like type A cells, but not in those of fibroblast-like type B cells from the synovial tissues or leucocytes from the synovial fluids. Longitudinal studies showed that the ir-ET-1 concentration in the cultured fluid reached a peak around 24 h after starting the culture. ET-1 secreted from macrophage-like synoviocytes may be involved in the pathogenesis of inflammatory arthritis.

2021 ◽  
Vol 11 ◽  
Author(s):  
Yeyong Zhang ◽  
Shufeng Li ◽  
Feng Zhuo ◽  
Hongxing Wang ◽  
Xiubin Geng ◽  
...  

AimThis study is to investigate the additive effect of Vitamin D-binding protein (VDBP) and 1,25(OH)2D3 on the viability and apoptosis of synovial cells from patients with rheumatoid arthritis (RA).MethodsSynovial tissues and synovial fluid of patients with RA and osteoarthritis (OA) were collected. The expression of VDBP was analyzed with immunohistochemistry and ELISA. CCK-8 assay was applied to detect cell viability. Flow cytometry was used to analyze cell cycle and apoptosis.ResultsImmunohistochemical results showed that the expression of VDBP in the synovium of RA patients was significantly lower than that of OA (P<0.05). Similarly, ELISA results presented a lower expression of VDBP in the synovial fluid of RA patients. The results of CCK-8 assay showed that both 1,25(OH)2D3 and VDBP significantly inhibited the viability of rheumatoid arthritis synovial fibroblasts (RASF) (P<0.05). The treatment with 1,25(OH)2D3+VDBP led to more significantly inhibited viability of RASF, compared with 1,25(OH)2D3 alone (P<0.05). The results of flow cytometry showed that 1,25(OH)2D3 and VDBP both promoted the apoptosis of RASF (P<0.05) and 1,25(OH)2D3+VDBP led to a higher proportion of RASF apoptosis, compared with 1,25(OH)2D3 alone (P<0.05). However, 1,25(OH)2D3 and VDBP had no significant effect on the cell cycle of RASF. Additionally, 1,25(OH)2D3 promoted the expression of VDBP in RASF, but not concentration-dependently.ConclusionVDBP is reduced in the synovial tissue and synovial fluid of RA patients and can inhibit viability of RASF and promote the apoptosis of RASF. The 1,25(OH)2D3 can upregulate the expression of VDBP in RASF. Additionally, VDBP can enhance the effects of 1,25(OH)2D3 on viability and apoptosis of RASF.


2019 ◽  
Vol 15 (4) ◽  
pp. 316-320
Author(s):  
Mir Amir Aghdashi ◽  
Seyedmostafa Seyedmardani ◽  
Sholeh Ghasemi ◽  
Zohre Khodamoradi

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objective: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 497.2-497
Author(s):  
J. Arroyo Palomo ◽  
M. Arce Benavente ◽  
C. Pijoan Moratalla ◽  
B. A. Blanco Cáceres ◽  
A. Rodriguez

Background:Musculoeskeletal ultrasound (MSUS) is frequently used in several rheumatology units to detect subclinical inflammation in patients with joint symptoms suspected for progression to inflammatory arthritis (IA). Synovitis grade I (EULAR-OMERACT combined score) is known to be a casual finding in healthy individuals, but studies headed to unravel its possible role on rheumatic diseases are sparse.Objectives:To investigate the correlation between synovitis grade I, and the diagnosis of IA made after a year follow-up period since MSUS findings, in patients of an MSUS-specialized unit of a Rheumatology Department.Methods:We conducted a descriptive, retrospective and unicentric study. 30 patients were selected from the MSUS-specialized unit of our Rheumatology Department from July-18 to January-19. Patients presenting synovitis grade 0 (exclusively), 2 and/or 3 on combined score were excluded. Data collection at baseline included age, sex, immunological profile and previous physical examination to the MSUS findings, as well as the diagnosis made by the rheumatologist in 1-year visit follow-up: dividing the patient sample into two groups: those who were diagnosed with IA and those not. Non-parametric statistical tests for comparing means were used.Results:The mean age was 51,6 years and 70% were females. 6 (20%) patients were diagnosed with inflammatory arthritis after a year follow-up: 2 (4,8%) psoriatic arthritis, 1 (3,3%) undifferentiated arthritis, 1 (3,3%) rheumatoid arthritis, 1 (3,3%) Sjögren’s syndrome. Non-inflammatory arthropathies were also found 24 (80%), of which, 12 (40%) were non-specific arthralgias and 8 (19%) osteoarthritis.In the group of patients who did not developed an IA the mean C-reactive protein (CPR) value was 3,12 mg/L and erythrocyte sedimentation rate (ESR) was 8,2 mm; all of them were rheumatoid factor (RF) positive and ACPA-negative except one patient. 5 (31,3%) patients presented low antinuclear antibodies (ANAs) levels. In those who HLA B-27 and Cw6 were tested (4,25%); both were negative except for one that was HLA B-27 positive. The median number of swollen and painful joint count was 0, and the mean of joints with MSUS involvement was 3,5; the mean involved metacarpophalangeal (MCP) joints was 1,83; proximal interphalangeal (PIP) joints was 1,48 and distal interphalangeal (DIP) joints 0,21.Among the group of patients that developed an IA the mean of CPR and ESR was 9,27 mg/L and 14,17 mm respectively; 2 (33%) patients were RF- positive, and 1 ACPA-positive. ANAs were positive in 3 cases (50%). The median of swollen joint count was 2 and for painful joint count was 0, the median of joints with MSUS involvement was 4,5. The mean of MSUS involvement was for MCP, PIP and DIP joints: 1,67, 2 and 0. Comparing the means of CPR values in the two groups with Student’s t-test we obtained a statistically significant difference (p=0,023). No other significant differences were found.Conclusion:Despite the limitations and possible statistical bias, the presence of MSUS-defined synovitis grade I and elevated CRP levels could be related to further diagnoses of inflammatory arthropathy. Besides, the absence of synovitis in DIP joints might have a diagnostic role. Normal physical exploration and normal levels of CRP might suggest low MSUS value. However, further research is needed to clarify the role of MSUS-defined synovitis grade I.References:[1]D’Agostino MA et al. Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 1: definition and development of a standardized, consensus-based scoring system. RMD Open. 2017;3(1):e000428.[2]Van den Berg R et al. What is the value of musculoskeletal ultrasound in patients presenting with arthralgia to predict inflammatory arthritis development? A systematic literature review. Arthritis Research & Therapy (2018) 20:228.Disclosure of Interests:None declared


Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ana Cecilia Machado Diaz ◽  
Araceli Chico Capote ◽  
Celia Aurora Arrieta Aguero ◽  
Yunier Rodríguez Alvarez ◽  
Diana García del Barco Herrera ◽  
...  

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA) in samples of synovial fluid from patients with RA and osteoarthritis (OA). The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.


2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.


Author(s):  
Anda Kadiša ◽  
Zaiga Nora-Krūkle ◽  
Svetlana Kozireva ◽  
Simons Svirskis ◽  
Pēteris Studers ◽  
...  

Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease affecting joints and causing symmetrical chronic progressive aseptic synovitis and erosive-destructive changes. Viruses and viral infections are considered to be the main risk factors for autoimmune disease development (especially for individuals with genetic predisposition). The goal of this study was to evaluate the frequency of HHV-6 and HHV-7 persistent infection and its activity phase in RA and osteoarthritis (OA) patients, and healthy persons. We examined also the influence of HHV-6 and -7 infections on RA activity, aggressiveness, radiographical stage, and frequency of complications as well as the presence of HHV-6 infection markers in synovial fluid and synovial tissues of RA joints of affected patients. Despite the lack of significant correlation between frequency of persistent single HHV-6, single HHV-7, and concurrent HHV-6 and HHV-7 infection and RA clinical course, we found that both active and latent HHV-6 and/or HHV-7 infection increased RA activity and progression in several clinical and laboratory parameters. Regarding the severity of the course of RA, we observed also a high prevalence of RA complications in the patient group with active single HHV-6 infection and also a more severe radiographical stage in RA patients with active concurrent HHV-6 and HHV-7 infection. Moreover, viral infection markers were found in synovial fluid and synovial tissues of affected joints of RA patients. This suggests that HHV-6 and/or HHV-7 infection has effect on the disease clinical course, but virus reactivation may be a consequence of immunosuppressive treatment.


2020 ◽  
Vol 142 (11) ◽  
Author(s):  
Elizabeth Feeney ◽  
Devis Galesso ◽  
Cynthia Secchieri ◽  
Francesca Oliviero ◽  
Roberta Ramonda ◽  
...  

Abstract Inferior synovial lubrication is a hallmark of osteoarthritis (OA), and synovial fluid (SF) lubrication and composition are variable among OA patients. Hyaluronic acid (HA) viscosupplementation is a widely used therapy for improving SF viscoelasticity and lubrication, but it is unclear how the effectiveness of HA viscosupplements varies with arthritic endotype. The objective of this study was to investigate the effects of the HA viscosupplement, Hymovis®, on the lubricating properties of diseased SF from patients with noninflammatory OA and inflammatory arthritis (IA). The composition (cytokine, HA, and lubricin concentrations) of the SF was measured as well as the mechanical properties (rheology, tribology) of the SF alone and in a 1:1 mixture with the HA viscosupplement. Using rotational rheometry, no difference in SF viscosity was detected between disease types, and the addition of HA significantly increased all fluids' viscosities. In noninflammatory OA SF, friction coefficients followed a typical Stribeck pattern, and their magnitude was decreased by the addition of HA. While some of the IA SF also showed typical Stribeck behavior, a subset showed more erratic behavior with highly variable and larger friction coefficients. Interestingly, this aberrant behavior was not eliminated by the addition of HA, and it was associated with low concentrations of lubricin. Aberrant SF exhibited significantly lower effective viscosities compared to noninflammatory OA and IA SF with typical tribological behavior. Collectively, these results suggest that different endotypes of arthritis exist with respect to lubrication, which may impact the effectiveness of HA viscosupplements in reducing friction.


2010 ◽  
Vol 391 (5) ◽  
pp. 571-579 ◽  
Author(s):  
Urška Požgan ◽  
Dejan Caglič ◽  
Blaž Rozman ◽  
Hideaki Nagase ◽  
Vito Turk ◽  
...  

Abstract Cysteine cathepsins and matrix metalloproteases are considered to play important roles in the development of arthritic diseases. Their accumulation in synovial fluid of primarily rheumatoid arthritis patients is also well documented. However, a detailed comparison between the protease levels and activities between rheumatoid arthritis samples and osteoarthritis samples has never been made. Here, we report that both cysteine cathepsins B and S and matrix metalloproteases-1, -3 and -13 are detected in patient synovial fluid samples with significantly higher levels detected in rheumatoid arthritis patients. Among the proteases, cathepsin S was found to be significantly elevated, consistent with its critical role in the immune response. These results suggest that cysteine cathepsins have a major role in inflammation at least in rheumatoid arthritis. In addition to proteases, interleukin-6 was detected at significant levels in most samples, suggesting that proinflammatory cytokines might be in-volved in the stimulation of expression of these proteases during inflammation.


2020 ◽  
Author(s):  
Hongxing Wang ◽  
Hui Wu ◽  
Kehua Fang ◽  
Xiaotian Chang

Abstract Background: Uridine diphosphate (UDP) is an extracellular nucleotide signaling molecule implicated in diverse biological processes via specific activation of pyrimidinergic receptor P2Y, G Protein-Coupled, 6 (P2Y6). There is very little knowledge about the function and mechanism of UDP in rheumatoid arthritis (RA).Methods: This study used a quasi-targeted liquid chromatography-mass spectrometry (LC-MS) approach to investigate the unique expression of metabolites in RA synovial fluids (SF) (n = 10) with samples from osteoarthritis (OA) as controls (n = 10). RA fibroblast-like synoviocytes (FLSs) were collected from synovial tissues (n = 5) and cultured with UDP or MRS2578, a P2Y6 antagonist, and FLSs from OA were used as controls (n = 5). Rats with collagen-induced arthritis (CIA) were injected with UDP, MRS2578 or both (n = 9 for each group). P2Y6 expression was examined using real-time PCR, Western blotting and immunohistochemistry. Cell proliferation, apoptosis and migration of RA FLSs were measured using CCK-8 assay, real-time cell analysis, flow cytometry, wound healing assay and Transwell assay, respectively. The UDP levels in the culture medium, synovial fluid (n = 36) and peripheral blood (n = 36) of RA and CIA rats were measured using a Transcreener UDP Assay. Levels of proinflammatory cytokines were measured using a flow assay. Interleukin-6 (IL-6) levels were measured using ELISA and flowResults:LC-MS analysis detected significantly increased UDP levels in RA SF compared with OA SF, and the level was positively correlated with anticyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) levels in RA. The increased UDP concentration was verified in the blood and synovial fluids of RA patients compared with samples from OA patients and healthy volunteers, respectively. UDP stimulated cell proliferation, migration and IL-6 secretion in RA FLSs and inhibited their apoptosis in culture, and MRS2578 inhibited these effects of UDP. UDP injection accelerated CIA and stimulated IL-6 production rather than other proinflammatory cytokines in the rat model, but simultaneous injection of MRS2578 suppressed these effects and alleviated CIA. P2Y6 expression was increased in RA and CIA synovial tissues.Conclusion: These results suggest that UDP is highly expressed in RA and stimulates RA pathogenesis by promoting P2Y6 activities to increase IL-6 production.


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