• 동의생리병리학회지
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• 제22권4호
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• pp.871-877
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• 2008

Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses and mediators of inflammation. HO-1 has been recently implicated in regulation of angiogenesis via expression of VEGF. The purpose of this study was to determine the effects of HO-1 modulation on the collagen-induced arthritis (CIA) model and on angiogenesis via up- regulation of VEGF expression in human synovial fibroblast. DBA/1J mice were treated with an inhibitor of HO-1, tin protoporphyrin IX (SnPP), or with an inducer of HO-1, cobalt protoporphyrin IX (CoPP), from day 1 to day 35 after CIA induction. The clinical evolution of disease was monitored visually. At the end of the experiment, histopathologic changes were examined on the joints. VEGF expression in paws were measured by immunohistochemical stain. mRNA expression of HO-1 and VEGF stimulated with various concentration of $TNF-{\alpha}$, CoPP accessed on human synovial fibroblast by RT-PCR. Effects of pretreatment with SnPP on mRNA expression of HO-1 and VEGF in the presence of CoPP and $TNF-{\alpha}$ in synovial fibroblast was accessed by Real-time RT-PCR. Administration of cobalt protoporphyrin IX significantly induced the inflammatory response, with increased arthritis index and expression of VEGF in the paws of the arthritis models. Treatment with SnPP significantly reduced the severity of CIA through inhibition of joint inflammation and cartilage destruction. The expression of VEGF were also significantly reduced by SnPP treatment in the paw. CoPPIX as inducer of HO-1, increased HO-1 and VEGF expression dose dependently in synovial fibroblast. In contrast, inhibition of HO-1 activity by SnPPIX abrogated CoPPIX-induced HO-1 and VEGF production in synovial fibroblast. Stimulation with $TNF-{\alpha}$ increased HO-1 and VEGF expression itself and showed additive effect on HO-1 and VEGF expression when it treated with CoPP. When SnPP was treated with CoPP and $TNF-{\alpha}$, it abrogated the CoPP induced HO-1 and VEGF expression and also abrogated $TNF-{\alpha}$ induced HO-1 and VEGF expression in synovial fibroblast. The effects of HO-1 induction in rheumatoid arthritis results in aggravation of arthritis via up-regulation of VEGF. I concluded that inhibition of the expression or activity of HO-1 could be a therapeutic target of rheumatoid arthritis.

• 한국축산식품학회:학술대회논문집
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• 한국축산식품학회 2006년도 정기총회 및 제37차 춘계 국제학술발표대회
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• pp.122-127
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• 2006

The innermost structures of synovium consist of one to three layers of cells generally identified as synovial lining cells(SLC). The present studies were initiated to determine the protein expression patterns of fibroblast-like synovial(FLS) cells derived from the synovia of rheumatoid arthritis. Post-traumatic arthritis(PTA) is one of the most common causes of secondary osteoarthritis, and usually affects younger people. The proteins were separated by two-dimensional polyacrylamide gel electrophoresis and RNA expression investigated by RT-PCR Proteome analyses led to the identification of more than 1,500 protein spots and of 11 differently expressed protein spots among them. Six proteins were down-regulated, and five proteins were up-regulated in ACL-transected synovial tissue. Among these, spots 3 and 8 were identified as cofilin-1 and smooth muscle protein $22-\alpha$, respectively, Therefore, the proteome analysis of synovial tissue is a useful approach to investigate a joint after an injury and can be used to understand the pathogenesis of PTA.

• Molecules and Cells
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• 제19권2호
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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 Acupuncture Research
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• 제18권1호
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• pp.113-128
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• 2001

Objective : To investigate the effect of BUM aqua-acupuncture in treating the RA, the immunosis to logical analysis of LPS induced arthritis in mice to study this. For 14th day after the injection of LPS & BUM injection, the distribution of fibroblast, collagen, CD54(ICAM-1), CD106(VCAM-1), IL-$1{\beta}$, IL-2 receptor, CDl lb(macrophage) were examined on synovial capsule of mice knee joint. For 14th day after the injection of LPS & BUM injection, the distribucion of CD4(TH cell), CD8(TC cell), CD40(B cell) were examined on common iliac lymph node in mice. Methods : The experimental model of arthritis was induced by injection of 300${\mu}g$/kg LPS in BALB/c mice weighing 30g. The 100${\mu}l$ BUM aqua-acupuncture which compounded calculus bovis, fel ursi and moschus was injected into GB34 of mice every other day for 12 days. For 3rd, 7th, 14th day after the injection of LPS, the neutrophil, lymphocyte and monocytc counts in WBC were measured using hemacytometer. Results : The obstain results are summarized as follows ; 1. In sample group, the neutrophils counts were increased and the lympnocytes counts were decreased compared with control group. 2. The distribution of fibrosis & fibroblast on synovial membrane were decreased compared with control group. 3. The distribution of collagen fiber on synovial membrane were decreased compared' with control group. 4. The distribution of CD54(ICAM-1) & CD106(VCAM-1) on synovial membrane were decreased compared with control group. 5. The distribution of IL-$1{\beta}$ & IL-2 receptor on synovial membrane were decreased compared with control group. 6. The distribution of CDb(macrophage) on synovial membrane were decreased compared with control group. 7. The distribution of CD4(TH cell), CD8(TC cell) and CD40(B cell) in common iliac lymph nodes were decreased compared with control group. Conclusions : BUM aqua-acupuncture stimulation decreased inflammatory responses LPS induced arthritis in mice.

• 대한세포병리학회지
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• 제4권2호
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• pp.171-175
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• 1993

Synovial sarcoma us a rare malignant neoplasm of the soft tissue arising in the lower extremity, inguinal area, and upper arm. The majority occurs in patients between the age of 15 and 40 years. The histologic diagnosis is based on the classical biphasic type with the distinct epithelial and spindle cell components. We have recently encountered a case of metastatic synovial sarcoma of the lung diagnosed by fine needle aspiration cytology. A 34-year-old man was admitted because of a palpable mass on the antero-lateral side of the right tibia for 3 years. On admission, a well demarcated metastatic pulmonary nodule, measuring 5 cm in diameter, was also identified in the simple chest X-ray. Resection of the lower leg mass revealed typical histologic features of biphasic synovial sarcoma. Aspiration cytology of the pulmonary nodule revealed numerous clusters of spindle cells admixed with groups of epithelial cells. The epithelial cells had moderate-sized, round to oval shaped, and hyperchromatic nuclei. The cytoplasm was clear, but not distinctive. Interspersed tell elements were fibroblast-like spindle cells having elongated hyperchromatic nuclei.

• Tuberculosis and Respiratory Diseases
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• 제45권6호
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• pp.1284-1289
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• 1998

저자들은 59세 여자환자에서 조직학적으로 면역학적으로 이상성 활막육종의 형태를 가진 원발성 폐육종 1예를 경험하였기에 이를 문헌 고찰과 함께 보고하는 바이다.

• 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.

• IMMUNE NETWORK
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• 제2권4호
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• pp.208-216
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• 2002

Background: Reactive oxygen and nitrogen are produced by rheumatoid arthritis (RA) synovial tissue and can induce mutations in key genes. Normally, this process is prevented by a DNA mismatch repair (MMR) system that maintains sequence fidelity. Key members of the MMR system include MutS${\alpha}$ (comprised of hMSH2 and hMSH6), which can sense and repair single base mismatches and 8-oxoguanine, and MutS${\beta}$ (comprised of hMSH2 and hMSH3), which repairs longer insertion/deletion loops. Methods: To provide further evidence of DNA damage, we analyzed synovial tissues for microsatellite instability (MSI). MSI was examined by PCR on genomic DNA of paired synovial tissue and peripheral blood cells (PBC) of RA patients using specific primer sequences for 5 key microsatellites. Results: Surprisingly, abundant MSI was observed in RA synovium compared with osteoarthritis (OA) tissue. Western blot analysis of the same tissues for the expression of MMR proteins demonstrated decreased hMSH6 and increased hMSH3 in RA synovium. To evaluate potential mechanisms of MMR regulation in arthritis, fibroblast-like synoviocytes (FLS) were isolated from synovial tissues and incubated with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP). Western blot analysis demonstrated constitutive expression of hMSH2, 3 and 6 in RA and OA FLS. When FLS were cultured with SNAP, the RA synovial pattern of MMR expression was reproduced (high hMSH3, low hMSH6). Conclusion: Therefore, oxidative stress can relax the DNA MMR system in RA by suppressing hMSH6. Decreased hMSH6 can subsequently interfere with repair of single base mutations, which is the type observed in RA. We propose that oxidative stress not only creates DNA adducts that are potentially mutagenic, but also suppresses the mechanisms that limit the DNA damage.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.405-413
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• 2020

Fibroblast-like synoviocytes (FLS) play a crucial role in initiating rheumatoid arthritis. B-cell activating factor (BAFF) plays a role in FLS survival as well as in B cell maturation and maintenance. Here, we investigated whether tumor necrosis factor (TNF)-α-induced BAFF expression controls FLS migration and whether BAFF expression in FLS could be regulated by KR33426 which is the inhibitor of BAFF binding to BAFF receptors (BAFF-R) by using MH7A synovial cells transfected with the SV40 T antigen. More TNF-α-treated cells migrated compared to the control. TNF-α increased BAFF expression in FLS, significantly. FLS migration was inhibited by the transfection with BAFF-siRNA. KR33426 also inhibited BAFF expression increased by TNF-α treatment in FLS as judged by western blotting, PCR, and transcriptional activity assay. Kinases including JNK, p38 and Erk were activated by TNF-α treatment. While JNK and p38 were inhibited by KR33426 treatment, no changes in Erk were observed. Transcription factors including p65, c-Fos, CREB and SP1 were enhanced by TNF-α treatment. Among them, c-Fos was inhibited by KR33426 treatment. Small interference(si)-RNA of c-fos decreased BAFF transcriptional activity. FLS migration induced by TNF-α was inhibited by the transfection with BAFF-siRNA. KR33426 increased Twist, Snail, Cadherin-11 and N-Cadherin. In contrast, KR33426 decreased E-cadherin and TNF-α-enhanced CCL2. Taken together, our results demonstrate that synovial cell migration via CCL2 expression could be regulated by BAFF expression which is decreased by KR33426 and c-Fos-siRNA. It suggests for the first time that the role of BAFF-siRNA on FLS migration might be matched in the effect of KR33426 on BAFF expression.

• Journal of Acupuncture Research
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• 제19권2호
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• pp.164-176
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• 2002

Objective : This research carried out to find out the effective efficiency of acupuncture at ST36 GB39 and herbal-acupuncture using different concentrational Uris Fel Bovis Calculus on adjuvant arthritis in rats. Method : In this study, I do acupuncture treatment and herbal-acupuncture in ST36 GB39 by solution that diluted to fivefold and tenfold with combined solution of Bovis Calcuclus and Ursi Fel at 10:1. And then I observed the change of inhibitory rate of paw edema, body weight, hematologic assay, histologic assay. Result : 1. In Adjuvant Arthritis in rats, the herbal-acupuncture group 1 is more efficienct then acupuncture group. 2. In histologic assay of knee joint, synovial cell and fibroblast markedly activated in herbal-acupuncture group. 3. The albumin level in serum more markedly increased in herbal-acupuncture group 2 than the control group. 4. The paw edema significantly decreased in acupuncture group and herbal-acupuncture group 2 compared with the control group. 5. The body weight significantly increased in acupuncture group and herbal-acupuncture group 2 compared with the control group. Conclusion : In these results, The herbal-acupuncture using Ursi Fel, Bovis Calculus, suppress inflammation of Adjuvant Arthritis, and decrease markedly the count of WBC, and increase the albumin level in serum, and have an influence on Adjuvant Arthritis with activating of synovial cell, fibroblast. And these were more effective than the others, and then needed consistent study of its mechanism.