• IMMUNE NETWORK
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• v.6 no.1
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• pp.20-26
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• 2006

Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease that is characterized by invasive synovial hyperplasia, leading to progressive joint destruction. Recent studies have described that RA is caused by virus, bacteria or outside material. Approximately 2 to 20% of RA cases arc reported to be associated with infected hepatitis C virus (HCV). However, the mechanisms underlying virus-induced RA are still unknown. Moreover, few molecular studies have addressed the inflammatory aspects of HCV-associated autoimmune RA. In this study, we aimed to determine whe ther or not another HCV core protein transactivates the IL-8 gene expression, prototypic chemokine, in synovial cell. Methods: To establish the HCV core expressing stable synovial cell line, pCI-neo-core, a plasmid encoding HCV core protein, were transfected to HIG-82 cell line that is an established cell line from rabbit periaricular soft tissue. We examined the morphological changes and cell cycle distribution of HIG-82 cells with expression of HCV core protein by inverted microscopy and flow cytometry analysis, respectively. Also, we determined the mRNA levels of Interleukin (IL)-6 and IL-8 related to the inflammation by RT-PCR and then analyzed regulation of IL-8 expression by the NF-${\kappa}B$ pathway. Results: Our study showed no significant differences in morphology and cell cycle between HIG-82 control cell line and HIG-82 expressing HCV core protein. However, expression of HCV core protein induces the IL-8 mRNA expression in HIG-82 core cells via activated NF-${\kappa}B$ pathway. Conclusion: These results suggest that HCV core protein can lead to enhanced IL-8 expression. Such a proinflammatory role may contribute to the etiologic pathogenesis in RA patients with HCV infection.

• Journal of Veterinary Clinics
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• v.24 no.3
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• pp.325-330
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• 2007

This study was to determine whether canine model which produce acute permanent joint instability in short period without postoperative exercise have a degenerative changes and also evaluated its suitability as an appropriate animal OA models. Ten skeletally mature beagle dogs underwent a unilateral surgical transection of the cranial cruciate ligament and, the medial collateral ligament as well as a medial meniscectomy. The contra-lateral joint was used as control. After 12 weeks, After 12 weeks, the amount of joint damage, inflammation and biochemical change of synovial fluid was evaluated. Histological analysis showed chondrocyte clone formation, hypertrophy of the cartilage and moderate loss of proteoglycans in the experimental joints compared to control joints. In addition, the synovial inflammation in the experimental joints was observed. Biochemical analysis of SF showed significantly increased MMP (matrix metalloproteinase) -2 and -9 in experimental joints compared to control joints. This canine OA model shows the characteristics of degenerative joint disease, and may have a advantages of reducing the time and cost because postoperative exercise is not needed in this OA model.

• 대한핵의학회:학술대회논문집
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• 1999.05a
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• pp.196-199
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• 1999

Radiation synovetomy with various radiopharmaceuticals has been used to alleviate pain and swelling of rheumatoid arthritis and related joint diseases for more than 40 years. It is an attractive alternative to the surgical synovectomy for the management of the various joint diseases. Recently, the development of new radiopharmaceuticals labeled with $^{90}Y,\;^{32}P,\;^{186}Re,\;^{188}Re,\;^{153}Sm,\;^{165}Dy$ and $^{166}Ho$, for the effective management of synovial inflammation and related arthritic problems are gaining attention. In this article the general concepts and the clinical application of radiation synovectomy are reviewed.

• The Journal of Dong Guk Oriental Medicine
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• v.7 no.2
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• pp.107-120
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• 1999

Synovial joint of BALB/C mice were injeced with Lipopolysaccharide(LPS) were observed to investigate the morphological changes of synovial capsule caused by rheumatoid arthritis(RA). The RA on female Balb/c mice were induced by LPS injection, as dose of $300{\mu}{\ell}/kg$, into synovial cavity of knee joint. And then these specimen were fixed in 10% neutral buffered formalin and were decalcificated in EDTA solution for 4 weeks. The hyperplasia of synovium were appeared in synovial membrane. The filopodia of phagocytic like synoviocyte(type I synoviocyte) projected into synovial cavity and the number of fibroblast like synoviocyte(type II synoviocyte) with well-developed endoplasmic reticulum were increased in synovium. In fibrous membrane, the fibrosis induced by synthesis of collagen fiber were enlarged to all fibrous membrane, and the number of fibroblast were increased. A great number of inflammation component cell as lymphocyte and neutrophil leukocyte were infiltrated around capillary and the degranulate typed mast cell were increased. As results indicated that the hyperplasia of synovium induced by LPS, subsequently to cause the fibrosis, infiltration of imflammation component cell, and increase of degranulated type mast cell as same as symptoms of RA.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.127-133
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• 2017

Background: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. Methods: The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis $factor-{\alpha}/interferon-{\gamma}-treated$ synovial cells, and HEK293 cells transfected with various inducers of inflammation. Results: G-Rc significantly inhibited the expression of macrophage-derived cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$. G-Rc also markedly suppressed the activation of TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells. Conclusion: G-Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling.

• The Journal of Korean Medicine
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• v.34 no.1
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• pp.116-135
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• 2013

Objectives: This study was intended to clarify how Jakyakkamchobuja-tang (hereinafter referred to JKBT) affects mice of C57BL/10 whose osteoarthritis was induced by papain. Methods: Osteoarthritis was induced in mice by injecting papain in the knee joint. Mice were divided into 4 groups (n=6). The normal group were not treated at all whereas the control group (OAC-control) were induced for osteoarthritis by papain and oral medicated with 200 ul of physiological saline per day. The positive comparison group (OAC-$Joins^{(R)}$) were injected with papain and after 7 days, 100 mg/kg of $Joins^{(R)}$ were medicated with 200 ul of physiological saline mixed. The experimental group (OAC-JKBT) were injected with papain and after 7 days were medicated with 400 mg/kg of JKBT mixed with 200 ul of physiological saline. OAC-$Joins^{(R)}$ and OAC-JKBT were oral medicated for each substance for a total of 4 weeks, once per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the function of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological variations for knee joint structures were observed. Results: Functions of liver and kidney were not affected. IL-$1{\beta}$ (interleukin-$1{\beta}$), MCP-1 (monocyte chemoattractant protein-1) and TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) were significantly reduced and IL-6 (interleukin-6) was also reduced but not significantly. After analyzing inflammation cytokine in joints with mRNA (messenger ribonucleic acid), revelation of IL-6, TNF-${\alpha}$, COX-2 (cyclooxygenase-2) and iNOS-II (inducible nitric oxide synthase-II) were all significantly reduced. Revelation of IL-$1{\beta}$ gene was also reduced but not significantly. Neutrophil for WBC (white blood cell) within serum was significantly reduced; monocyte was also reduced but not significantly. PGE2 (prostaglandin E2), TXB2 (thromboxane B2) were significantly reduced and LTB4 (leukotriene B4) was also reduced but not significantly. Destruction of cartilage on micro CT (computed tomography)-arthrography was reduced but had no significant differences. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small (H&E (hematoxylin and eosin), safranine O staining). Conclusions: Based on these results, Jakyakkamchobuja-tang (JKBT) is believed to be useful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

• The Journal of Dong Guk Oriental Medicine
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• v.9
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• pp.35-49
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• 2000

Purpose: This study is to investigate the alleviation effects of Daebangpoongtang in LPS induced arthritis in mice knee joint. Methods : Daebangpoongtang was chosen to treat the arthritis caused by injecting $300{\mu}g/kg$ LPS to mice knee joint. The control group had no treatment, while the LPS group was injected $300{\mu}g/kg$ LPS to mice knee joint and the DBP group was oral administrated of Daebangpoongtang. After injection of $300{\mu}g/kg$ LPS to mice knee joint, the alteration of synovial lining cell, vessel, fibrosis, distribution of collagen fiber, fibroblast, mast cell, infiltration of inflammation component cell and distribution of ICAM and VCAM was observed by light microscope(BX50). Results : In the DBP extract treatment group, the distribution of vessel, the enlargement of synovial lining cell layer, the synovial lining cells with filopodia, the fibrosis, the distribution of fibroblast in synovial membrane, the distribution of TCAM and VCAM on the knee joint was less than that of LPS group. Infiltrated lymphocyte into the apical surface had not observed in the DBP extract treatment group. The distribution of mast cell was as same as control group(no treatment group) and it showed granulated type. Conclusion: According to the above results, it might be considered that the administration of Daebangpoongtang has a curative effect on synovial membrane injury in arthritis by inhibiting increase of vessel, cell adhesion molecule(ICAM and VCAM) in LPS induced arthritis.

• The Journal of Korean Medicine
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• v.34 no.3
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• pp.69-85
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• 2013

Objectives: This study investigated the anti-osteoarthritic effects of Kyejiinsam-tang (hereinafter referred to KIT) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods: Anti-oxidative effects of KIT were measured by scavenging activities of DPPH, reactive oxygen species (ROS) and nitric oxide (NO). Scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cells were also measured for inhibitory effects against the production of inflammatory mediators (tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6). Osteoarthritis was induced in rats by injecting MIA in the knee joint. Rats were divided into a total of 4 groups (n=6). The normal group were not treated at all without inducing osteoarthritis whereas the control group were induced for osteoarthritis by MIA and oral medicated physiological saline per day. The positive comparison group was injected with MIA and after 7 days, 2 mg/kg of Indomethacin. The experimental group was injected with MIA and after 7 days was medicated with 34 mg/kg of KIT. Indomethacin and KIT were orally-medicated for each substance a total of 4 weeks, once per day. Weight-bearing on hind legs was measured every week after MIA injection. At the end of the experiment (5 weeks after MIA injection), micro CT (computed tomography)-arthrography and histopathological examinations on the articular structures of knee joint were performed. The effect on inflammatory cytokines and immunological cells in synovial fluid was measured. Volume of cartilage was measured by micro CT-arthrography. Injury to synovial tissue was measured by H & E (hematoxylin and eosin), Safranin-O immunofluorescence. Results: 1. Cytotoxicity against hFCs was insignificant. 2. KIT showed the potent full term for DPPH. 1. NO was significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and ROS was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 2. IL-6 and IL-$1{\beta}$ were significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and TNF-${\alpha}$ was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 1. In hind legs weight-bearing measurement, level of weight increased. 2. Functions of liver and kidney were not affected. 3. IL-$1{\beta}$ was significantly reduced and TNF-${\alpha}$, IL-6 were also reduced but not significantly. 4. PGE2 (prostaglandin E2), LTB4 (leukotriene B4) were significantly reduced in the KIT group. 5. MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinases-1) and Osteocalcin were significantly reduced in the KIT group. 6. Destruction of cartilage on micro CT arthrography was reduced but had no significant differences. 7. Histopathologically, injury to synovial membrane of the KIT group was decreased and proteoglycan content of KIT group was increased. Conclusions: According to this study, Kyejiinsam-tang has inhibiting effect on the progression of arthritis in MIA-induced osteoarthritis rat. Kyejiinsam-tang has anti-oxidants and anti-inflammation effects, and is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• Journal of Acupuncture Research
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• v.24 no.4
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• pp.167-181
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• 2007

Objectives: To evaluate expression of MIF mRNA, MIF, $TNF-{\alpha}$, $IL-6R-{\alpha}$, STAT-3, $NF-{\kappa}B$ p65, COX-2 and iNOS, MMP-9mRNA after injecting deer antler herbal acupuncture solution in a LPS rat model. Methods: The experiment was divided in category of the control group, RA group, and NA group. RA was induced in the mice via injecting 300ug/kg LPS. The deer antler herbal acupuncture solution 50ug/kg was applied on $ST_{35}$(犢鼻) and EX-LE201(內膝眼) for 19days from $3^{rd}$ day of RA inducement. Results: 1. In the deer antler herbal acupuncture solution treated RAW 264.7cell, the mRNA expression of cytokines, RA related inflammation factors, such as the MIF, COX- 2, iNOS, and MMP-g reduced concentration dependently. 2. In the deer antler herbal acupuncture treated mice's synovial membrane, decrease in the cell replication of synovial joint cells, regeneration of blood vessel, fibrosis and fibroblastic cells expansion were observed. 3. Positive reaction of RA-related cytokines MIF, $TNF-{\alpha}$, $IL-6R-{\alpha}$, STAT3, COX-2, iNOS, $NF-\;{\kappa}B$ p65, MMP-9 was reduced. Conclusion : On the basis of the results, it was concluded that deer antler herbal acupuncture extract has significant protecting ability against acute progressive RA by inhibiting the production of MIF, as a top in cytokines related to inflammation.

• The Korean Journal of Nuclear Medicine
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• v.29 no.1
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• pp.84-91
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• 1995

Many clinical and laboratory tests have been employed to evaluate disease activity in rheumatioid arthritis. $^{99m}Tc$-labelled polyclonal IgG(HIG) has been demonstrated to accumulate in focal sites of infection or inflammation in both animals and human subjects. The purpose of this study was to distinguish arthritis with active inflammation from those without active inflammation and to correlate relative intensities of $^{99m}Tc$-labelled HIG uptake of the rheumatoid arthritis with clinical and MR indices of the joint inflammation. This study included twelve patients with active rheumatoid arthritis, two with ankylosing spondylitis and one with degenerative osteoarthritis without active inflammation. A Whole-body and spot images were obtained 4 hours after intravenous injection of 20mCi of $^{99m}Tc$-labelled HIG. Scintigrams were assessed visually by 3 experienced radiologists, and graded as normal or mildly and markedly increased uptake within the joints, and the degree of uptake was compared with clinical and radiologic severity of synovial inflammation. MRI studies were done on the involved joints consisted of wrist(n = 11), knee(n = 2) and hip joint(n= 2). Active synovitis was defined when marked elevation of ESR and gadolinium enhancement of synovium on MRI were demonstrated. Markedly increased radiotracer uptake was seen in 10 of 11 rheumatoid arthritic patients with active synovitis whereas normal or mildly increased uptakes were noted in others, including rheumatoid arthritic patient(n=1) and non-rheumatoid patients(n = 3) without active synovitis. This study showed that the localization of involved joints in rheumatoid arthritis could be detected with $^{99m}Tc$-labelled HIG and that the degree of uptake correlated well with the degree and activity of inflammation. In conclusion, $^{99m}Tc$-labelled HIG scan is a useful method in the evaluation of active inflammation in rheumatoid arthritis.