• 대한바이러스학회지
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• 제28권3호
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• pp.267-274
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• 1998

Human cytomegalovirus (HCMV) has the ability to activate the expression of many viral and cellular genes. Among various viral proteins, the immediate early proteins (IE1-72kDa, IE2-86kDa) have been known to be potent transactivators. The product of c-jun proto-oncogene is important in cell activation and differentiation. Here, we tried to find out if the IE could activate the c-jun promoter and also tried to identify the responsible sequence elements in the c-jun activation by IE1-72kDa. We found HCMV IE expression transactivated the c-jun promoter in human embryonal lung fibroblasts (HEL). The activation fold by IE1-72kDa, IE2-86kDa and IE2-55kDa was 23, 35, and 5, respectively. When the expression of each IE was combined, it showed synergism. Expression of (IE1-72kDa + IE2-86kDa) and (IE1-72kDa + IE2-86kDa + IE2-55kDa) resulted in 131 and 162 fold increase, respectively. The c-jun promoter region between -117 and -59 contains binding sites for the transcription factors Spl, CAAT, AP-l like (ATF/CREB), and MEF2. Transient expression assays were performed using various reporter plasmids containing the c-jun promoter-regulatory region linked to the luciferase gene and a plasmid expressing HCMV IE1 gene. Deletional and point mutational analysis showed that the sequence between -225 to -160 and the CTF binding site were involved in the up-regulation of c-jun promoter.

• Biomolecules & Therapeutics
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• 제20권5호
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• pp.463-469
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• 2012

Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.

• Childhood Kidney Diseases
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• 제1권2호
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• pp.130-135
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• 1997

목적 : Interleukin-6는 광범위한 영역의 조직과 세포의 성장과 분화에 영향을 미치는 다기능 사이토카인으로 사구체 메산지움 세포의 성장도 관여하는 것으로 알려져 있다. 메산지움 세포의 증식과 IgA의 침착을 특징으로 하는 IgA 신병증에서 IL-6가 메산지움 세포의 성장 인자임이 입증되었고 요중 IL-6치가 메산지움 증식의 정도나 예후 판정에 유용한 것으로 알려져 있다. HSP 신염은 병리조직학적으로나 임상적으로 IgA 신병증과 유사해 HSP 신염에서도 IL-6가 병리 기전에 관여할 것이 예상되므로 HSP 신염 환아에서 IL-6의 의의에 대해 알아보고자 하였다. 방법 : 대상 환아는 연세대학교 의과대학 영동 세브란스 병원 소아과에 입원한 HSP 환아 30명과 HSP 신염환아 18명 및 정상 대조군 10명으로 혈청 및 요중 IL-6치를 ELISA 방법으로 측정하였다. 결 과 : HSP 환아, HSP 신염 환아 및 정상 대조군의 혈청 IL-6치는 각각 $36.03{\pm}87.56pg/ml,\;32.68{\pm}71.59pg/ml,\;3.17{\pm}3.78pg/ml$로 HSP 환아와 HSP 신염 환아에서 정상 대조군에 비해 유의하게 증가되어 있었으며 (p<0.05), 요중 IL-6치는 HSP 신염 환아에서 $62.23{\pm}73.53pg/ml$로 HSP 환아($9.05{\pm}8.35pg/ml$)와 정상 대조군($5.83{\pm}5.62pg/ml$)에 비해 의미있게 증가된 소견을 보였다.(p<0.05). HSP 신염 환아에서 24시간 요단백량과 요중 IL-6치는 24시간 요단백량이 증가할수록 요중 IL-6치가 통계학적으로 유의하게 중가하였으나며(y=51.923x-45.091, $R^2=0.6185$, p=0.0014), 혈청 IL-6치와 요중 IL-6치간에는 유의한 상관 관계는 없었다. 결론 : IL-6는 IgA 신병증에서와 마찬가지로 HSP 신염에서 메산지움 증식에 연관이 있는 것으로 사료되며 경과나 예후 판정에 유용한 보조 지표가 될 수 있는 지에 대한 추후 관찰이 요할 것으로 사료된다.

• 생명과학회지
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• 제18권12호
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• pp.1637-1643
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• 2008

HSP90에 노출된 혈관평활근세포에서 IL-6 transcript가 증가하고, IL-6 단백질의 분비가 증가하며, 또한 IL-6 유전자의 promote가 활성화되었다. HSP90에 의한 IL-6 유전자의 promoter 활성화는 dominant negative 형태의 TLR-4와 MyD88에 의하여 크게 감소되었지만, dominant negative 형태의 TLR-3와 TRIF의 영향을 받지 않았다. 그리고 TLR-4의 이합체화(dimerization)를 저해하는 curcumin은 HSP90에 의한 IL-6의 분비 및 IL-6 유전자 promoter 활성화를 억제하였다. 그리고 IL-6 유전자의 promoter의 NF-${\kappa}B$- 또는 C/EBP-binding sequence에 변이는 HSP90에 의한 IL-6 유전자의 promoter 활성화 억제하였다. 이러한 결과는 혈관평활근세포에서 HSP90에 의한 IL-6 유전자 활성화에 TLR-4와 NF-${\kappa}B$B가 관여함을 의미한다.

• 생명과학회지
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• 제21권6호
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• pp.783-787
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• 2011

3T3-L1 지방전구세포 분화 억제에 대한 Thaumatococcus daiellii 열매 유래 토마틴의 항비만 효과를 검토하였다. 3T3-L1 지방전구세포에 토마틴을 0-5 ${\mu}M$ 농도로 처리한 결과 세포생존율은 처리 농도 의존적으로 감소하였는데, 토마틴 8일 처리 후 1 및 3 ${\mu}M$ 농도에서 각각 97% 및 88.3%의 세포생존율을 보였다. 또한 토마틴 3 ${\mu}M$ 처리 농도에서 Oil-Red-O염색 지방구가 현저히 감소된 것으로 나타났다. 3T3-L1 세포 내 중성지방 농도는 양성 대조군에 비해 농도 의존적으로 감소하였다. 따라서 천연 식물성 토마틴은 3T3-L1 지방전구세포의 세포증식 억제 및 중성지방 농도 감소 효과를 보여 항비만 효과가 있는 것으로 밝혀졌다.

• 한국식품위생안전성학회지
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• 제28권2호
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• pp.188-193
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• 2013

Aphanizomenon flos-aquae는 시아노박테리아 일종이며 anatoxin-a, saxitoxin, neosaxitoxin 등의 독소를 생산할 수 있어 국내에서는 식품원료로 사용이 금지되어있다. 전통적으로 시아노박테리아는 사상체 넓이, 세포 크기, 분열방법, 세포형태, 가스주머니의 존재유무 등의 형태학적 특징에 의한 분류가 가능하다. 그러나 가스주머니 혹은 무성포자와 같은 특징은 주변 환경 또는 생장조건에 따라 차이가 있으며 경우에 따라 소실되기도 한다. 따라서 PCR에 의한 Aph. flos-aquae를 함유하는 기능식품을 검출할 수 있는 분석법을 개발하였다. 프라이머를 설계하기 위하여 유전자은행(www.ncbi.nlm.nih.gov)에 등록되어있는 Aph. flos-aquae, 스피루리나의 16S rRNA 염기서열을 이용하였으며, 비교 및 분석에는 BioEdit ver. 7.0.9.0 프로그램을 사용하였다. 최종적으로 클로렐라, 스피루리나, 녹차, 시금치로부터 Aph. flos-aquae를 검출할 수 있는 AFA-F1/AFA-R1(363 bp) 프라이머를 최종 선정하였다. 그리고 상기 프라이머는 Aph. flos-aquae가 각각 1% 함유 되도록 제조된 클로렐라, 스피루리나 제품에서 모두 혼입여부의 확인이 가능함을 확인하였다.

• Archives of Plastic Surgery
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• 제38권2호
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• pp.131-134
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• 2011

Purpose: Stem cells continue to receive research attention in the clinical fields, and adipose-derived stem cells (ADSCs) have been shown to be a good source raw material. Many plastic surgeons are researching the ADSC adipogenesis with a view of conducting clinical trials, and many attempts have been made to identify the factors that promote the adipogenesis of ADSCs, but comparatively few correlation studies have been undertaken to explore the relation between reactive oxygen species (ROS) and the ADSC adipogenesis. We undertook this study is to investigate the effects of ROS on ADSC adipogenesis. Methods: ADSCs were isolated and cultured from abdominal adipose tissue, and cultured in different media; 1) DMEM(control), 2) adipogenesis induction culture medium, 3) adipogenesis induction culture medium with ROS ($20{\mu}M/50{\mu}M\;H_2O_2$), 4) adipogenesis induction culture medium containing ROS ($20{\mu}M/50{\mu}M\;H_2O_2$) and antioxidant ($10{\mu}M/20{\mu}M$ Deferoxamine). We compared adipogenesis in these different media by taking absorbance measurements after Oil-Red O staining every 5 days. Results: After culturing for 20 days, significant differences were observed between these various culture groups. Absorbance results showed significantly more adipogenesis had occurred in media containing adipogenesis induction culture medium and $H_2O_2$ (in a $H_2O_2$ dose-dependently manner) than in media containing adipogenesis induction culture medium and no $H_2O_2$ (p<0.001). Furthermore, in media containing adipogenesis induction culture medium, $H_2O_2$, and antioxidant, absorbance results were significantly lower than in adipogenesis induction culture medium and $H_2O_2$ (p<0.001). Conclusion: These findings suggest that ROS promote the adipogenesis of ADSCs. We suggests that ROS could be used in the adipose tissue engineering to improve fat cell differentiation and implantable fat tissue organization.

• 동의생리병리학회지
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• 제20권3호
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• pp.548-556
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• 2006

This study was to evaluate the effect of Samjayangchin-tang (STYCT) on mouse Th1 and Th2 cells' differentiation and ovalbumin (OVA)-induced allergic inflammation. The proliferation of mouse CD4 T cells and the secretion of Th1/Th2 cytokines under the influence of STYCT extract were measured as well as the amount of ${\beta}-hexosaminidase$ in RBL-2H3 cells and the levels of $TNF-{\alpha}$ and IL-6 secretion in Raw264.7 cells. BALB/c mice were orally administered with STYCT extract and simultaneously inoculated with OVA to induce allergic reaction and measure the level of total IgE, OVA-specific IgE and the production of IFN- g, IL-4, IL-5 by the spleen cells. When mouse CD4 T cell were stimulated with anti-CO3 and anti-CD28 for 48 hours in various concentrations of STYCT extract, it decreased proliferation of CD4 cells. CD4 T cells under Th1/Th2 polarizing conditions for 3 days with STYCT resulted in mild decrease of IFN- g in Th1 cells and significant decrease of IL-4 in Th2 cells. STYCT extract had a dose-dependent inhibitory effect on antigen-induced release of ${\beta}-hexosaminidase$ in RBL-2H3 cells. Treatment of STYCT extract on LPS stimulated Raw 264.7 cells showed dose-dependent decrease in IL-6 production. Oral administration of STYCT extract on OVA-induced allergic mice showed an inhibitory effect on the levels of total serum IgE and OVA-specific IgE by 53% and 44%, respectively. Culture of spleen cells with OVA resulted in significant increase of IFN- g by 54% and significant decrease of IL-4 and IL-5 by 42%, and 29%, respectively. The results show that STYCT does not strongly induce mouse T cells to transform into Th1 or Th2 but it has an anti-allergic effect in vitro, and that it also corrects the unbalance between the reactions of Th cells in allergic diseases.

• 대한수의학회지
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• 제36권1호
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• pp.151-159
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• 1996

This study was carried out to evaluate the effects of all-trans retinoic acid(RA) on the development of cholangiocarcinoma in hamsters. Eighty six female Syrian golden hamsters were divided into four groups. Group I was for the induction of the cholangiocarcinoma, which was infected orally with C sinensis and given dimethylnitrosamine(DMN, 15ppm) in drinking water for 4 weeks. Group II was for evaluating the effect of all-trans RA treatment on the cholangiocarcinogenesis, which was treated the same as group I and orally given RA(1mg/kg, 5 times per week) for 15 weeks. Group III was given only RA hr 15 weeks. Control group IV was given only soybean oil which was solvent for RA treatment. More than 5 heads of hamsters in each group were sacrificed at 4, 7, 11 and 15 weeks after the begining of the experiment. The livers were examined grossly, histopathologically, and immunohistochemically. The results obtained were as follows : 1. Death of animals started from the 11 weeks after the begining of the experiment. One of the total 22 animals(5%) and 7 of the total 24 animals(29%) died in group I and group II, respectively. 2. Proliferation of oval cell was peaked at 11 weeks in group I and at 7 weeks in group II, and decreased gradually after those periods of the time. 3. Cholangiocarcinomas were found in 1 of 6 animals(17%) at 11 weeks and in 4 of 6 animals(67%) at 15 weeks in group I, respectively. But in group II, the cholangiocarcinomas occured in 1 of 5 animals(20%) at 7 weeks, in 7 of 12 animals(58%) at 11 weeks and in 2 of the rest animals(100%) at 15 weeks, respectively. 4. Expression of $\alpha$-fetoprotein(AFP) of the oval cells in the group II showed the same degree of positive reaction at that of group I at 4 weeks. But AFP postive oval cells decreased gradually and AFP negative oval cells(ductlike oval cells) increased gradually. 5. Expression of cytokeratin of the oval cells in group II was shown slightly at 4 weeks and the degree of expression increased moderately from the 7 weeks. But the expression of the oval cells in group I was shown slightly after the 7 weeks. These results suggested that all-trans RA promoted the occurrence and the rate of cholangiocarcinoma by inducing differentiation of small cells and oval cells in the liver of hamsters infected with C sinensis and treated with DMN.

• 대한핵의학회지
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• 제17권1호
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• pp.1-10
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• 1983

Carcinoembryonic antigen (CEA) levels were measured in the serum of 35 normal control subjects and 179 cases of various benign and malignant gastrointestinal diseases. Malignant gastrointestinal tumors include 69 cases of stomach cancer, 24 cases of hepatoma and 33 cases of colorectal cancer. Benign gastrointestinal diseases include 29 cases of peptic ulcer and 24 cases of liver cirrhosis. The results were as followings: 1) Mean serum CEA level in normal control subjects was $6.9{\pm}3.3ng/ml$ and there was; no difference in mean serum CEA level between age and sex difference. 2) In malignant gastrointestinal tumors, mean serum CEA level in colorectal cancer, hepatoma and stomach cancer, were $54.3{\pm}88.9ng/ml,\;62.1{\pm}99.7ng/ml$ respectively. Serum CEA level showed positive rate of 67% in colorectal cancer, 63% in hepatoma and 62% in stomach cancer. There was no difference in mean levels and positivity of serum CEA between these 3 malignant tumor groups. 3) Positivity of serum CEA was 61% in malignant gastrointestinal tumor group in spite of 37% in benign gastrointestinal disease group. In both mean level and positivity of serum CEA, stomach cancer was much higher than peptic ulcer. But there was no difference in mean level and positivity of serum CEA level between hepatoma and liver cirrhosis. 4) In hepatoma serum CEA level showed positive rate of 62.5% and alpha-feto protein showed a rate of 58.3%. 5) Mean serum CEA levels in patients with cancer in rectal, cecal, sigmoid colon, ascending: colon and descending colon were $73.7{\pm}106.7ng/ml,\;69{\pm}84.8ng/ml$, $15.7{\pm}9.1ng/ml,\;7.5{\pm}10.6ng/ml$ and 4.0ng/ml respectively. Positive rate of serum CEA showed 86% in sigmoid. colon cancer, 68% in rectal cancer and 66% in cecal cancer. 6) In considering of histological background, there was no correlation between the degree of differentiation of tumor cell and the serum CEA level in colorectal cancer. According to Duke's classification, the mean serum levels of CEA were $8.8{\pm}11.4ng/ml$ in group A, $15.3{\pm}16.0ng/ml$ in group B and $68.5{\pm}101.5ng/ml$ in group C respectively. Positivity-of serum CEA in group A, Band C were 40%, 50% & 69% respectively. So there was significant correlation between the degree of elevation of serum CEA and tumor extension.