• IMMUNE NETWORK
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• 제6권1호
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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.

• 한국임상수의학회지
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• 제24권3호
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• pp.325-330
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• 2007

본 연구는 개에서 수술적으로 짧은 기간 동안 관절의 불안정성을 최대로 유도하여 수술후 운동 없이 관절의 퇴행성 변화의 유무 및 정도와 골관절염 모델로 적합한지를 평가 하였다. 10두의 비글견을 본 실험에 사용하였다. 실험군은 오른쪽 무릎관절의 앞십자인대 및 내측 곁인대의 절제와 내측 반월 연골 절제술을 시행하였으며, 왼쪽 무릎관절을 대조군으로 사용하였다. 수술 12주 후 연골의 손상, 윤활막의 염증 정도와 윤활액의 생화학적 변화를 평가 하였다. 조직 검사에서 연골의 비후, 연골 세포의 분화, 프로테오글리칸의 소실 및 윤활막의 염증이 대조군과 비교하여 유의성 있는 증가가 관찰되었다. 윤활액의 생화학적 검사에서 유의성 있게 증가된 MMP-2, -9의 농도를 실험군에서 관찰 하였다. 이상의 결과로부터 본 연구에 수행한 관절염 모델은 골관절염 유도가 가능하며, 술후 운동으로 소모되는 시간 및 비용을 줄 일수 있는 장점 있어 골관절염 모델로서 유용하게 활용될 것으로 판단된다.

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 1999년도 제38차 춘계학술대회
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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.

• 동국한의학연구소논문집
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• 제7권2호
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• pp.107-120
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• 1999

본 연구는 관절염 유발시 일어나는 관절낭의 형태학적 변화를 조사하기위해 lipopolysaccharide(LPS) 주사로 인위적 관절낭 염증을 유발시킨 후 시간경과에 따른 윤활관절막과 섬유관절막의 향태 변화를 관찰하였다. BALB/C 암컷 생쥐 오른쪽 무릎관절낭에 LPS $300{\mu}g/kg$를 주사한 후 3, 7 그리고 14일에 무릎관절을 얻었다. 무릎관절은 4주동안 EDTA용액에 탈회한 후 통상적 방법으로 paraffin에 포매하였다. 또한 윤활관절막의 미세구조변화는 embed812로 포매한 후 관찰하였다. LPS 주사후 관절연골인접부위의 윤활관절막에서 시작된 세포과형성(hyperplasia)은 시간 경과후 전체 윤활관절막으로 확대되었다. 윤활관절막내의 미세구조의 변화로는 윤활포식세포(type I)가 관절강내로의 많은 돌기(filopodia)를 내었고, 잘 발달된 과립형질내세망을 가지는 type 2 윤활분비세포의 숫적 증가가 보였다. 한편 LPS 주사후 섬유관절막에서 나타나는 형태학적 변화는 collagen fiber 생성에 의한 섬유화가 증가되며, 이러한 섬유화를 주도하는 섬유모세포의 이주증가가 관찰되었다. 또한 혈관 주위에서는 백혈구의 이주 증가가 나타났으며, 탈과립형(degranulated type) 비만세포가 많이 관찰되었다. 이상의 결과로 LPS 주사로 관절낭에서 염증이 유발되어 윤활관절막과 섬유관절막에서 헝태학적 변화가 나타났다. 이러한 일련의 형태학적 변화는 발병초기 류마티스성 관절염에서 나타나는 병리학적 소견과 동일한 결과로서, 앞으로 진행될 치료제 개발과 유발기전에 관한 해석을 위한 in vivo 실험의 적절한 모델로 기여할 것으로 기대된다.

• Journal of Ginseng Research
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• 제41권2호
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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.

• 대한한의학회지
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• 제34권1호
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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.

• 동국한의학연구소논문집
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• 제9권
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• pp.35-49
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• 2000

본 실험은 대방풍탕(大防風湯)이 혈관생성과 세포유착인자발현 억제를 통해 LPS(lipopolysaccharide)유발 관절염 완화에 미치는 영향을 조사하기 위해 LPS주사로 관절염이 유발된 생쥐에게 대방풍탕(大防風湯) 추출액을 음용 투여하였다. 실험동물은 20g된 female Balb/c계 생쥐암컷을 선별하여 아무런 처치를 하지 않은 대조군, 무릎관절에 LPS를 주사한 LPS군, LPS주사후 대방풍탕(大防風湯) 추출액을 투여한 DBP군으로 나누어, 다시 LPS와 DBP군은 LPS처리 후 시간의 경과에 따라 3, 7, 14일로 구분하였으며, 실험군 각각에는 실험동물을 10마리씩 배정하였다. 광학 현미경(BX50)으로 대방풍탕(大防風湯) 추출액 투여가 LPS주사 후 증가된 윤활 관절막내 혈관분포 증가에 미치는 영향과 아울러 윤활세포, 섬유화 및 섬유모세포, 비만세포와 염증관여세포, 세포유착인자 등의 윤활 관절막에서의 형태변화를 관찰하였다. DBP군에서는 자유면에서 윤활세포과형성의 억제와 침윤 림프구의 감소, 낮은 섬유화 양상과 침적 섬유모세포의 감소, 모세혈관 주변의 림프구 침적 감소와 비만세포 분포감소, 자유면과 섬유지역분포ICAM과 혈관주변분포VCAM 등과 같은 세포유착인자의 감소 등이 관찰되었다. 이상의 결과로 볼 때 대방풍탕(大防風湯)은 관절염 유발시 발생되는 혈관생성과 세포유착인자의 발현증가 등을 억제함으로써 이후 발생되는 윤활 관절막 손상을 완화하는 것으로 사료된다.

• 대한한의학회지
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• 제34권3호
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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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• 제24권4호
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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.

• 대한핵의학회지
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• 제29권1호
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• pp.84-91
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• 1995

지금까지 류마티스 관절염의 염증 정도의 평가를 위하여 많은 검사들이 사용되어져 왔다. $^{99m}Tc$-labelled HIG 스캔은 동물실험과 사람에서도 염증이나 감염병소에 집적되는 것으로 알려져 있다. 본 연구의 목적은 $^{99m}Tc$-labelled HIG 스캔을 이용하여 류마티스 관절염 환자에서 활동성 염증이 있는 군과 없는 군을 구별해 보고자 하였고 이러한 결과를 다른 임상인자와 조영증강 자기공명영상과 비교해 보았다. 11명의 활동성 염증이 있는 류마티스 관절염 환자와 활동성 염증이 없는 류마티스 관절염 환자 1명, 강직성 척수염 환자 2명 그리고 퇴행성관절염 환자 1명을 대상으로 하였다. 활동성 염증(active synovitis)은 ESR의 상당한 증가와 조영증강 자기공명영상에서 조영증강을 보이는 경우로 정의하였다. $^{99m}Tc$-labelled HIG를 정맥주사후 4시간후에 전신 및 국소영상을 얻었다. 섭취정도의 평가는 3명의 전문의에 의하여 3단계로 나누어 시각적으로 평가하였다. 모든 환자에 있어서 조영증강 자기공명영상을 같이 시행하였다. 활동성 염증이 있는 11명의 류마티스 관절염 환자중 10명에서 상당한 정도의 섭취증가를 보인 반면 활동성 염증이 없는 나머지 환자에서는 정상 또는 미미한 정도의 섭취증가만을 보였다. 본 연구에서 $^{99m}Tc$-labelled HIG 스캔을 이용하여 류마티스 관절염에 이환된 관절들의 전반적인 국소화가 가능하였고 $^{99m}Tc$-labelled HIG의 섭취정도가 다른 임상적이나 자기공명영상의 활동성 염증을 시사하는 인자들과 잘 연관되었다. 결론적으로 $^{99m}Tc$-labelled HIG 스캔은 류마티스 관절염 환자에 있어서 염증 정도를 평가해 볼 수 있는 유용한 방법이 될 수 있을 것으로 생각한다.