• Molecules and Cells
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• v.19 no.2
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• pp.180-184
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• 2005

IL-17 is a major proinflammatory cytokine secreted by activated T-lymphocytes that accumulates in the inflamed joints of rheumatoid arthritis (RA) patients. Additional IL-17-related molecules and their receptors have been discovered and may also contribute to RA pathogenesis. We examined the expression of the prototypic IL-17 (IL-17A) and its homologs, IL-17B-F, by RT-PCR analyses of synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from RA patients. We also tested for induction of the IL-17 receptor homologs upon stimulation of the fibroblast-like synoviocytes (FLSs) of RA patients with IL-17. The patients' SFMCs expressed IL-17C, E and F in addition to IL-17A. As in the case of IL-17, IL-15 appears to be the major inducer of these homologs in RA SFMCs. We detected transcripts of IL-17R, as well as those of IL-17RB, C and D, in the FLSs of RA patients. Whereas IL-17R expression increased upon in vitro stimulation with IL-17, expression of IL-17RB, C and D was unchanged. However the possibility of cross-interaction between other IL-17 homologs and receptor isoforms remains to be investigated. Our data suggest that these additional homologs should also be considered as targets for immune modulation in the treatment of RA joint inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1647-1655
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• 2005

Gamimahaenggamsuk-tang (GMHGST) is used for treatment of inflammatory diseases including rheumatoid arthritis (RA). Here, regulatory activity of GMHGST on RA-mediated inflammatory responses was investigated in cultured human fiDroblast-like synoviocytes (FLS), Levels of mRNAs encoding for inflammatory cytokines such as $IL-1{\beta}$, IL-6 and IL-8 and NOS-II enzyme, which had been induced by $TNF-{\alpha}$ and $IL-1{\beta}$ cotreatment, were decreased to the similar levels as those in cells treated with anti-inflammatory agent MTX. mRNA expressions of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases (TIMPs) as well as intercellular adhesion molecule (ICAM) were also downregulated by increasing doses of GMHGST in activated FLS. Moreover, GMHGST appeared to protect cells by decreasing NO levels, and inhibited cell proliferation which had been induced by inflammatory stimulation by $TNF-{\alpha}$ and IL-1. These results suggest that GMHGST is effective as an inhibitory agent for regulating inflammatory responses in activated FLS.

• Applied Microscopy
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• v.26 no.1
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• pp.11-16
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• 1996

This study was designed to observe the ultrastructure of synoviocytes which are concerned with phagocytic function in the knee joint of the human. The synovia were dissected and were fixed for two hours in 0.2% glutaraldehyde and 4% paraformaldehyde solution and processed and finally infused in 2.3 M sucrose and 20% PVP solution. The tissues were cut with the cryoultramicrotome and labelled with primary antibodies (anti-tubulin, anti-vimentin) and secondary antibody-6 nm colloidal gold particles. The tissues were observed under transmission electronmicroscope. The results were followings. 1. In phagocytic synovial cells, the distributions of tubulin were cytoplasm, especially around vacuoles. 2. In phagocytic synovial cells, the distributions of vimentin were cytoplasm. 3. Both tubulin and vimentin were not located inside of vacuoles. On the basis of above findings, it is obvious that the phagocytic functions are concerned with tubulin, and the phagocytic synovial cells contain vimentin.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.728-735
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• 2007

This study was carried out to know the effect of Gwanjulbang-5(hereinafter refer to GJB-5) to on Rheumatoid Arthritis by using human fibroblast-like synoviocytes(hFLS). We performed several experimetal items : that is cytotoxicity of GJB-5, mRNA expression of pro-imflammatory cytokines in hFLS and production of NO, ROS. The results were obtained as follows : GJB-5 reduced the production of pro-inflammatory cytokines TNF-${\alpha}$, IL-1${\beta}$, IL-6, IL-8 in hFLS, increased the production of TIMP-1. As well as GJB-5 reduced the production of ICAM-1, MMP-3, NOS-II, the production of NO and ROS, and the proliferation of hFLS in proportion to the concentration of GJB-5. In conclusion, these results shows that GJB-5 had immunomodulatory effects in treating rheumatoid arthritis.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.536-543
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• 2023

Phytoceramide (Pcer) is found mainly in plants and yeast. It can be neuroprotective and immunostimulatory on various cell types. In this study, the therapeutic effect of Pcer was explored using the carrageenan/kaolin (C/K)-induced arthritis rat model and fibroblast-like synoviocytes (FLS). Pcer treatment (1, 10, and 30 mg/kg/day) were given to the arthritic rats for 6 days after disease induction. Weight distribution ration (WDR), knee thickness, squeaking score, serum levels of proinflammatory mediators, and histological analysis were measured and performed to evaluate arthritic symptoms in the rat model. In interleukin (IL)-1β-stimulated FLS, proinflammatory mediators were measured after Pcer (1-30 µM) treatment. Arthritic symptoms in rats with Pcer treatment were significantly decreased at days 4 to 6 after C/K arthritis induction. Inflammation in the knee joints were also significantly decreased in rats with Pcer treatment. Furthermore, in IL-1β-stimulated FLS, the expressions of proinflammatory mediators were also inhibited by Pcer. As shown by the results, Pcer has anti-arthritic effects in the C/K rat model and in synovial cells, suggesting that Pcer has the potential to be a useful agent in arthritis treatment.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.168-168
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• 2023

• Journal of Ginseng Research
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• v.48 no.3
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• pp.346-346
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• 2024

• IMMUNE NETWORK
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• v.4 no.3
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• pp.190-197
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• 2004

Background: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic synovial inflammation which leads to joint destruction. Gene therapy of RA targets the players of inflammation or articular destruction. However, viral vectors have safety problems and side effects, while non-viral vectors suffer from inefficient gene transfer and fast loss of gene expression. To overcome the limits of non-vial vectors, an EBV-based plasmid which is known to exert prolonged high level gene expression can be used. Methods: pEBVGFP, pEBVIL-10, and pEBVvIL-10 were constructed by cloning GFP, IL-10, and vIL-10 genes into an EBV-based plasmid, respectively. The pGFP was used as a control plasmid. Each constructs were lipofected into HIG-82 rabbit synoviocytes. The expression of GFP was monitored by FACS and confocal microscopy. IL-10 and vIL-10 expressions were measured by ELISA. Results: GFP expression 2 days after transfection was achieved in 33.2% of cells. GFP-expressing cells transfected with pGFP decreased rapidly from 4 days after transfection and disappeared completely by 11 days. Cells transfected with pEBVGFP began to decrease slowly from 4 days. But GFP expression was detected for over 35 days. In addition, HIG-82 cells transfected with pEBVIL-10 ($44.6{\pm}1.5ng/ml$) or pEBVvIL-10 ($51.0{\pm}5.7ng/ml$) secreted these cytokines at high levels. High level cytokine production by hygromycin selection was maintained at least for up to 26 days after transfection. Conclusion: These results suggest that the EBV-based plasmid has a potential to improve non-viral gene transfer system and may be applicable to treat RA without the drawbacks of viral vectors.

• The Korean Journal of Pain
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• v.13 no.1
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• pp.1-7
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• 2000

Background: Intraarticular local anesthetic injection has been therapeutically applied for pain control in various arthritis patients. However, little physiologic effects of local anesthetics on their tissue were known. This study was conducted to determine its effects on the cell proliferation and matrix metalloproteinases (MMP) production of cultured fibroblast like synoviocytes (FLS) derived from synovial tissues of rheumatoid arthritis patients. Methods: Bupivacaine with varying concentrations 0 (control), 0.1, 0.25, 0.5% was applied to experimental cell groups growing as monolayers in culture plates for varying durations 0 (control), 30, 90, 180 seconds in the presence and absence of interleukin-$1\beta$. Results: No statistical significances were noted in thymidine incorporation between 0, 30, 90 and 180 seconds exposure groups with 0.5% bupivacaine after 1 day and 2 days. Thymidine incorporation between 0, 0.1, 0.25, 0.5% exposure groups 1 day and 2 days after 90 seconds exposure did not show any differences. After exposure to bupivacaine, there were statistically significant increases in MMP-1 (p=0.025) and MMP-3 productions (p=0.000) of FLS in the absence of IL-$1\beta$, but no differences among the groups in the presence of IL-$1\beta$. Conclusion: We concluded that in this short-term in vitro study, bupivacaine does not have injurious effect on cultured rheumatoid arthritic joint tissues. The long-term effect cannot be known from this investigation.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.88-106
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• 2006

Objectives: This study was carried out to find the immune responses of the Gami-sopunghwalhyeol-tang $(Ji{\={a}}w{\`{e}}i-sh{\={u}}f{\={e}}nghu{\'{o}}xu{\`{e}}-tang)$ (hereinafter referred to GSHT) to the human fibroblast-like synoviocytes (hFLSs) isolated from patients with rheumatoid arthritis. Methods: Experiments were performed to measure the cytotoxity against hFCs and the production of pro-inflammatory cytokines in hFLSs and the production of NO, ROS. Results: 1. The gene expression of TNF-a, IL-6, IL-8 in hFLSs was effectively reduced at $100{\mu}g/ml$, whereas IL-1 $\beta$ was effectively reduced at 100 and $10{\mu}g/ml$ of GSHT. 2. The gene expression of ICAM-1, MMP-3 in hFLSs was effectively inhibited at 100 and $10{\mu}g/ml$ of GSHT, whereas TIMP-1 was effectively increased at 100 and $10{\mu}g/ml$ of GSHT. 3. The gene expression of NOS-II in hFLSs was effectively inhibited at $100{\mu}g/ml$ of GSHT. 4. The production of NO and ROS in hFLSs was inhibited at 100 and $10{\mu}g/ml$ of GSHT. 5. The proliferation of hFLSs was significantly inhibited at $100{\mu}g/ml$ of GSHT. Conclusions: Comparison of the results for this study showed that Gami-sopunghwalhyeol-tang ($Ji{\={a}}w{\`{e}}i-sh{\={u}}f{\={e}}nghu{\'{o}}xu{\`{e}}-tang$: GSHT) had immunomodulatory effects of suppressing or enhancing.