• Journal of Periodontal and Implant Science
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• 제31권3호
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• pp.611-623
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• 2001

Cyclosporin A is a cyclic polypeptide produced by the metabolism of fungi. It is widely used at present as immunosuppressive treatment following organ transplants. It is also used to deal with autoimmune diseases such as rheumatoid arthritis or type II diabetes. Gingival hyperplasia is one of the most frequent side-effects associated with the prescription of Cyclosporin A. The mechanisms involved in Cyclosporin A induced gingival hyperplasia are not yet clear. In vitro Cyclosporin A promotes proliferation of gingival fibroblasts, that Cyclosporin A act as a mitogen. Its action is based on mitosis of gingival fibroblasts regulated by cell cycle regulatory proteins. It was the purpose of the present study to examine the effects of Cyclosporin A on human gingival fibroblasts by means of biological and biochemical criteria. In this present study, we examined change of cell proliferation, cell activity, cell viability and cell cycle progression after application of Cyclosporin A. We also examined expression of cell cycle regulatory proteins by western blot analysis. Human gingival fibroblasts were cultured for 48 hours with application of Cyclosporin A at concentrations of 0.01, 0.1, 1, and 10 ng/ml. Cyclosporin A(1 ng/ml) significantly increased the cell activity of gingival fibroblast. Proliferation and viability of gingival fibroblasts were also increased in group treated with 1 ng/ml of Cyclosporin A compared to control group. In the cell cycle analysis, S phase was increased and G1 phase was decreased in the group treated with 1 ng/ml of Cyclosporin A. Cyclosporin A increased the expression of cdk4 and inhibited the expression of pRB and p21. These results suggest that 1 ng/ml of Cyclosporin A may increase the cell cycle progression of human gingival fibroblasts, and its mechanisms may increase the expression of cdk4 and decrease the expression of pRB and p21.

• International Journal of Oral Biology
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• 제36권4호
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• pp.173-178
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• 2011

Tumor necrosis factor alpha ($TNF{\alpha}$) is a multifunctional cytokine that is elevated in inflammatory diseases such as atherosclerosis, diabetes and rheumatoid arthritis. Recent evidence has suggested that ${\beta}2$ adrenergic receptor (${\beta}2AR$) activation in osteoblasts suppresses osteogenic activity. In the present study, we explored whether $TNF{\alpha}$ modulates ${\beta}AR$ expression in osteoblastic cells and whether this regulation is associated with the inhibition of osteoblast differentiation by $TNF{\alpha}$. In the experiments, we used C2C12 cells, MC3T3-E1 cells and primary cultured mouse bone marrow stromal cells. Among the three subtypes of ${\beta}AR$, ${\beta}2$ and ${\beta}3AR$ were found in our analysis to be upregulated by $TNF{\alpha}$. Moreover, isoproterenol-induced cAMP production was observed to be significantly enhanced in $TNF{\alpha}$-primed C2C12 cells, indicating that $TNF{\alpha}$ enhances ${\beta}2AR$ signaling in osteoblasts. $TNF{\alpha}$ was further found in C2C12 cells to suppress bone morphogenetic protein 2-induced alkaline phosphatase (ALP) activity and the expression of osteogenic marker genes including Runx2, ALP and osteocalcin. Propranolol, a ${\beta}2AR$ antagonist, attenuated this $TNF{\alpha}$ suppression of osteogenic differentiation. $TNF{\alpha}$ increased the expression of receptor activator of NF-${\kappa}B$ ligand (RANKL), an essential osteoclastogenic factor, in C2C12 cells which was again blocked by propranolol. In summary, our data show that $TNF{\alpha}$ increases ${\beta}2AR$ expression in osteoblasts and that a blockade of ${\beta}2AR$ attenuates the suppression of osteogenic differentiation and stimulation of RANKL expression by $TNF{\alpha}$. These findings imply that a crosstalk between $TNF{\alpha}$ and ${\beta}2AR$ signaling pathways might occur in osteoblasts to modulate their function.

• 대한본초학회지
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• 제25권2호
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• pp.129-136
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• 2010

Objective : Sinapis alba L. (SA) is a korean traditional herbal medicine that is usually used to prevent or treat inflammatory diseases, such as respiratory infection and rheumatoid arthritis. However, the effects of SA supplementation in vitro on serum antibody levels, splenocyte and peritoneal macrophage immune responses have not yet been determined. In this study, we examined the effect of SA on the production of Th1/Th2 cytokines. Methods : Splenocytes were isolated from naive C57BL/6 mice. Cells were enriched for CD4+ cell populations by first staining the cells with anti-CD4 (BD PharMingen, Calif, USA). CD4+ T cells were selected on a (CS) column, and the flow-through was collected as CD4+ T cells. Isolated cells were activated by overnight incubation on 24-well plates coated with $1{\mu}g/mL$ anti-CD3, $1{\mu}g/mL$ anti-CD28 and with SA ($100{\mu}g/mL$). Primary macrophages were collected from the peritoneal cavities of mice (8-week-old female C57BL/6). The peritoneal macrophages were washed and plated with RPMI-1640 overnight for the experiments. After 48-hours cultures, samples were centrifuged at 2000 rpm for 10 minutes, and the supernatants were stored at $-80^{\circ}C$. Mouse IL-4, IFN-$\gamma$ and TNF-$\alpha$ were quantified using ELISA kits (BioSource International, Camarillo, Calif, USA) according to the manufacturer's protocols. Results : SA at 100ug/ml decreased the generation of Th1 cytokine (IFN-$\gamma$) by 0.5-fold. However, SA has no effect on Th2 (IL-4) production. Conclusions : These results suggest that SA may play an important role in the control of T-cell-mediated autoimmunity by down-regulation of Th1 cytokine (especially IFN-$\gamma$, TNF-$\alpha$). These data may contribute to the design of new immunomodulating treatments for a group of autoimmune diseases.

• Tuberculosis and Respiratory Diseases
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• 제38권1호
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• pp.1-7
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• 1991

To study the frequency of the underlying disease of the diffuse pulmonary infiltrates in korea, we ansalyzed retrospectively 982 patients who were seen at nine university hospitals and one general hospital in Seoul area. The results are folloing: 1) Among the total 982 patients, 490 patients were male and 492 patients were female. The mean age was 44.3 years. 2) The most common etiology was milliary tuberculosis (38%), which was followed by, idopathic pulmonary fibrosis (27%), pulmonary fibrosis associated with collagen-vascular disease (15%), and diffuse pulmonary infiltrates by malignancy (10%). 3) Amon the connective tissue disease which was accompanied by the interstitial lung disease, rheumatoid arthritis was the most common disease (43%), systemic lupus erythematosus was the 2nd (28%), and progressive systemic sclerosis was the 3re (16%). 4) Among 101 cases of malignant disease, lung was the most frequent primary site (31%), which was followed by stomach (28%), thyroid (16%), and breast (6%). 5) For the diagnosis of the underlying disease of pulmonary infiltrates, the transbronchial lung biopsy was performed in 21% of the patients and open lung biopsy was done in 7%.

• Molecules and Cells
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• 제37권5호
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• pp.426-434
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• 2014

Peptidylarginine deiminase type 2 (PADI2) deiminates (or citrullinates) arginine residues in protein to citrulline residues in a $Ca^{2+}$-dependent manner, and is found in lymphocytes and macrophages. Vimentin is an intermediate filament protein and a well-known substrate of PADI2. Citrullinated vimentin is found in ionomycin-induced macrophage apoptosis. Citrullinated vimentin is the target of anti-Sa antibodies, which are specific to rheumatoid arthritis, and play a critical role in the pathogenesis of the disease. To investigate the role of PADI2 in apoptosis, we generated a Jurkat cell line that overexpressed the PADI2 transgene from a tetracycline-inducible promoter, and used a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin to activate Jurkat cells. We found that PADI2 overexpression reduced the cell viability of activated Jurkat cells in1a dose- and time-dependent manner. The PADI2-overexpressed and -activated Jurkat cells presented typical manifestations of apoptosis, and exhibited greater levels of citrullinated proteins, including citrullinated vimentin. Vimentin overexpression rescued a portion of the cells from apoptosis. In conclusion, PADI2 overexpression induces apoptosis in activated Jurkat cells. Vimentin is involved in PADI2-induced apoptosis. Moreover, PADI2-overexpressed Jurkat cells secreted greater levels of vimentin after activation, and expressed more vimentin on their cell surfaces when undergoing apoptosis. Through artificially highlighting PADI2 and vimentin, we demonstrated that PADI2 and vimentin participate in the apoptotic mechanisms of activated T lymphocytes. The secretion and surface expression of vimentin are possible ways of autoantigen presentation to the immune system.

• 한국식품과학회지
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• 제41권4호
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• pp.441-445
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• 2009

In vivo에서 10주간의 UV처리에 의해 유발되는 피부 손상에 대한 콜라겐 펩타이드 혼합물(AP-CPM01)의 보호 효능을 관찰한결과, UV에 의해 유도되는 주름의 증가와 탄력 저하 및 비정상적인 각질 세포의 증식에 의한 피부 두께의 증가가 혼합물의 섭취에 의해 개선됨을 확인하여, 콜라겐 펩타이드 혼합물이 UV에 의한 피부 손상을 방어하고, 피부 기능이 정상적으로 작용할 수 있도록 도움을 주는 것을 알 수 있었다. 콜라겐 펩타이드 혼합물의 피부 보호 작용 기전을 살펴보기 위하여 사람 섬유아세포를 이용하여 콜라겐 펩타이드 혼합물의 작용을 평가한 결과, 콜라겐 펩타이드와 엘라스틴 단백질은 procollagen 발현을 농도 의존적으로 증가시키고 시너지 효과가 있음을 확인하였으며, 이를 통하여 콜라겐 펩타이드 혼합물이 광노화에 의해 유발되는 피부 진피층의 손상을 회복 혹은 보호하는 효능이 있음을 알 수 있었다. 이상의 결과로부터 콜라겐 펩타이드 혼합물(AP-CPM01)이 광노화 보호 또는 피부 개선 효능을 갖는 새로운 미용 식품 소재로써 이용 가능성이 높음을 알 수 있다.

• 한국정보통신학회논문지
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• 제14권5호
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• pp.1209-1216
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• 2010

당뇨 합병증 등으로 인한 말초혈류 및 신경장애, 수족냉증 및 손가락 관절염, 통증 질환이 증가하고 있으며, 이러한 문제를 개선할 수 있는 손가락 질환 전용 치료기기가 전무한 상태로 이와 관련된 치료기의 개발이 필요하다. 본 연구에서는 시변 미약자기장을 이용하여 비침습적으로 말초혈류/신경개선과 손가락 류마티스 치료를 위한 솔레노이드 원통형 코일을 제작하고, 다양한 치료목적에 사용하기 위해서 3가지 자극모드(N, S, N/S)와 자극주파수(0.25, 0.5, 1hz)를 선택할 수 있는 시스템을 설계하였다. 자속밀도 측정 프로브를 솔레노이드의 중심에서부터 거리를 0 ~ 3cm 단계로 자극방식과 주파수별로 자속밀도를 측정하였다. 자속밀도를 측정한 결과, 모든 자극방식과 주파수에서 솔레노이드 내부의 중심(0cm)에 근접할수록 자속밀도가 급격히 증가하였다. 솔레노이드 중심 자속밀도는 N자극 (294.3mT)과 S자극(293.8mT)에서는 1Hz, N/S자극(275.4mT)에서는 0.25Hz에서 가장 높게 측정되었다. 본 논문에서는 다양한 패턴과 강도의 자기장을 이용하여 다양한 손가락 질환을 치료할 수 있는 솔레노이드형 치료기기를 개발하였다. 솔레노이드 내부 자속밀도를 측정함으로써 손가락 말초질환 개선을 위한 미약자기장 시스템의 임상 적용 가능성을 확인하였다.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.437-442
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• 2020

Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris. Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

• Journal of Nutrition and Health
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• 제46권2호
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• pp.186-196
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• 2013

The objective of this study was to develop a semi-quantitative food frequency questionnaire (FFQ) for an adult population for use in the Korea National Health and Nutrition Examination Survey (KNHANES). The 24-hour recall data for 2,939 subjects aged 19 years and over from the fourth KNHANES first year (2007) were used to extract the items included in the questionnaire. The FFQ items were developed by selection of major dishes based on the cumulative contribution rate, between-person variability based on the cumulative R2 of energy and 14 nutrients (carbohydrate, protein, fat, crude fiber, calcium, phosphorous, iron, sodium, potassium, vitamin A, thiamin, riboflavin, niacin, and vitamin C) and the number of consumers of each dish. In addition, the FFQ items were revised with analysis of 24-hour recall data of the fourth KNHANES second and third year (2008, 2009). Finally, 112 items were included in the FFQ and grouped as follows: rice (5 items), noodles and dumplings (6), breads and rice cakes (8), soups and stews (12), soybeans, eggs, meat and fish (23), vegetables, seaweed and potatoes (27), milk and dairy products (4), fruits (13), beverages (5), snacks (6) and alcoholic beverages (3). The food items of FFQ accounted for an average of 87.0% of energy and 14 nutrient intakes and also accounted for 81.7% of the between-person variability. The frequency range of the FFQ items was classified into nine categories (never or seldom, once per month, 2-3 times per month, once per week, 2-4 times per week, 5-6 times per week, once per day, twice per day and three times per day) and the portion size was divided into three categories (small, medium and large). We expect that this developed dish-based FFQ could be used in assessment of longterm dietary intakes of Korean adults.

• 한국식품과학회지
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• 제53권6호
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• pp.756-760
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• 2021

현재 시판되는 항생제 및 항결핵약제 대부분은 균의 성장을 저해하는 기전에 맞추어 개발되었고, 지금도 새로운 약제들이 개발되고 있다. 이러한 약제들은 사용빈도가 증가함에 따라 자연발생적으로 약제내성이 출현하게 되고, 약제 내성 결핵의 경우 치료가 더 어려울 뿐만 아니라 치료에 소요되는 시간과 비용이 기하급수적으로 증가한다. 이런 관점에서 볼 때, 인체 면역을 활성화시켜 결핵을 치료하는 방법이 결핵균을 직접적으로 사멸시키는 방법보다 더 안전하고 효과적인 방법이 될 수 있을 것이다. 본 연구에서는 오랜 시간 동안 민간요법으로 사용되어지고 있으면서 탐식구 활성화를 촉진시키는 것으로 알려져 있지만, 항결핵 효과는 검증되어 있지 않은 FRM에 의한 항결핵효과를 검증하였다. 유향의 세포독성효과를 확인하기 위해 MTT reduction assay를 실시하여 31.3, 62.5 ㎍/mL의 농도에서 독성효과를 나타내지 않는 것을 확인하였다. 또한 형태학적 관찰을 통해서도 세포독성 효과를 나타내지 않은 것을 확인하였다. 대식세포의 면역 작용기전을 측정하는 중요한 지표인 cytokine TNF-α, IL-1β의 발현양의 변화를 통해서 면역반응을 확인하였다. 결핵균이 감염된 대조군에서는 이 cytokine들의 발현이 증가한 반면, FRM을 처리한 세포에서는 발현이 감소하였고, 결핵균 또한 감소하였다. 이러한 현상은 FRM이 necrosis를 감소시키면서 apoptosis로 면역반응을 유도하여 발생하는 것으로 가정할 수 있으며, 결과적으로 결핵균 제거 효과를 보여주었다. 현재 치료가 힘든 다제내성결핵, 광범위내성결핵에서 유향이 대식세포의 면역력 활성화를 통한 항결핵효과를 나타내는 치료제로서의 잠재적인 가능성을 제시하였다. 다만, 추가적인 항결핵효과의 검증 및 면역기전에 대한 연구가 이루어져야 할 것으로 사료된다.