• 생명과학회지
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• 제20권5호
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• pp.655-661
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• 2010

흑색종세포주 SK-MEL-2에서 레티노이드에 의한 GD3합성효소(hST8Sia I)의 발현억제기작을 규명하게 위하여 hST8Sia I의 프로모터 활성을 조사해 본 결과 -1146에서 -646영역에서 레티노이드에 의한 활성억제를 나타내었다. 또한 부위특이적 변이와 ChIP분석은 -731에서 -722영역에 위치한 전사인자NF-kB 결합부위가 hST8Sia I의 레티노이드에 의한 활성억제에 중요하게 관여하고 있음을 나타내었다. 이러한 발현 억제는 PKC/ERK 신호전달경로를 통하여 일어난다는 것을 신호전달경로 저해제를 이용한 RT-PCR과 프로모터 활성조사에 의해 규명하였다.

• Molecules and Cells
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• 제41권7호
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• pp.653-664
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• 2018

The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their micro-environment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.

• 한국식품영양과학회지
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• 제46권11호
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• pp.1271-1277
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• 2017

가미십전대보탕(이하 KSD로 표기) 추출물은 생약 성분으로 인체 및 동물에 투여 시 세포 독성 및 장기에 중금속 등에 의한 독성 물질이 발생할 수 있어 안전성이 매우 중요하다. 따라서 본 연구에서는 KSD의 안전성 확보를 위해 중금속 검사, 간과 신장 기능 지표 검사 및 RAW 264.7 세포 생존 시험을 거친 후 RAW 264.7 세포를 이용하여 KSD 추출물의 항산화 및 항염증 효과를 알아보았다. KSD 추출물에서 중금속은 발견되지 않거나 기준치 미만으로 검출되었다. 간기능지표인 AST, ALT는 정상군에 비해 낮게 나타났으며 신기능 지표인 Cr, BUN도 정상군과 같거나 낮아 인체에 안전함을 확인하였다. RAW 264.7 세포 독성은 대조군 대비 농도별 생존율에 차이가 없었다. KSD 추출물의 항산화 효능 측정 결과 DPPH 라디칼 소거능과 ABTS 라디칼 소거능은 $10{\mu}g/mL$ 이상의 농도에서 의존적으로 활성이 증가하였다. 항염증 효과 측정 결과 NO 생성량은 대조군에 비해 10, $100{\mu}g/mL$에서 유의성 있는 감소를 보였으며, $IL-1{\beta}$와 IL-6는 농도 의존적으로 발현량이 감소하였고, $TNF-{\alpha}$는 유의적 차이점을 발견할 수 없었다. 이상의 결과를 보아 KSD는 골절 치료를 위한 생약으로 안전성 및 항산화 및 염증 감소에 효과가 있을 것으로 생각된다.

• 한국식품과학회지
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• 제46권4호
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• pp.505-510
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• 2014

본 연구는 고종시 감나무 부위별 수용성 추출물의 항산화 및 항염증에 대한 효과를 조사하였다. 감꼭지와 감잎은 DPPH, ABTS 및 NO 등 라디칼을 효과적으로 제거하는 활성뿐만 아니라 환원력도 우수한 항산화 활성을 보였다. 또한 LPS에 의해 활성화된 설치류 유래 대식세포주인 RAW 264.7 세포에서 NO 생성억제는 감꼭지 추출물이 가장 우수하였지만, $PGE_2$ 생성의 경우 모든 부위의 추출물에서 탁월한 억제 효과가 있었다. 더욱이 활성화된 RAW 264.7 세포에서 감꼭지, 감잎 및 감껍질 추출물은 농도에 의존적으로 TNF-${\alpha}$와 IL-$1{\beta}$를 효과적으로 억제하였다. 이러한 결과는 고종시 감나무 부위별 추출물 중 감꼭지와 감잎은 항산화제뿐만 아니라 항염증에 효과적인 물질이라는 것을 제시해주었고, 감껍질의 경우 비록 항산화 효과는 낮았지만, 우수한 항염효과를 나타내는 물질임을 제시해주었다. 그러므로 고종시 감나무 수용성 추출물은 항산화와 항염 기능을 발휘할 수 있는 식품으로 활용될 수 있을 것이라 사료된다.

• Journal of Microbiology and Biotechnology
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• 제18권7호
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• pp.1308-1316
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• 2008

Propionibacterium acnes is known to playa pivotal role in the pathogenesis of acne vulgaris. CBT-SL5 is one of the antimicrobial peptides from Enterococcus faecalis SL5, and it has shown antimicrobial activity against P. acnes. The aim of this study was to investigate the anti-inflammatory effect of CBT-SL5 on the inflammation induced by P. acnes in cultured human keratinocyes. Cultured human keratinocytes derived from neonatal foreskin were treated with heat-killed P. acnes to induce inflammation, and then various concentrations of CBT-SL5 were added to the P. acnes-treated keratinocytes. The mRNA expression and protein secretion of interleukin (IL)-8, an inflammation marker, was analyzed by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. We also analyzed the nuclear factor-kappa B (NF-$\kappaB$) p65 translocation by performing immunofluorescent staining. P. acnes treatment up regulated the IL-8 mRNA expression in the keratinocytes, and this was brought about through both toll-like receptor (TLR)2 and TLR4. At the concentrations of 10, 50, and 100 ng/ml, CBT-SL5 significantly down regulated the P. acnes-induced IL-8 mRNA expression and protein production (p<0.05). At 6 hand 12 h of the treatment, CBT-SL5 significantly suppressed the P. acnes-induced IL-8 mRNA expression. Secretion of IL-8 protein was significantly reduced at 24 h. The functional inhibitory activity of CBT-SL5 was shown by CBT-SL5 suppressing the P. acnes-induced NF-$\kappaB$ translocation from the cytoplasm to the nucleus. These results demonstrated that CBT-SL5 suppressed the P. acnes-induced IL-8 expression in keratinocytes. Therefore, CBT-SL5 may be a novel anti-inflammatory treatment for acne.

• Journal of Microbiology and Biotechnology
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• 제30권9호
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• pp.1412-1419
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• 2020

Human noroviruses (HuNoVs) are a leading cause of gastroenteritis outbreaks worldwide. However, the paucity of appropriate cell culture models for HuNoV replication has prevented developing effective anti-HuNoV therapies. In this study, first, the replication of the virus at various temperatures in different cells was compared, which showed that lowering the culture temperature from 37℃ significantly increased virus replication in Madin-Darby canine kidney (MDCK) cells. Second, the expression levels of autophagy-, immune-, and apoptosis-related genes at 30℃ and 37℃ were compared to explore factors affecting HuNoV replication. HuNoV cultured at 37℃ showed significantly increased autophagy-related genes (ATG5 and ATG7) and immune-related genes (IFNA, IFNB, ISG15, and NFKB) compared to mock. However, the virus cultured at 30℃ showed significantly decreased expression of autophagy-related genes (ATG5 and ATG7), but not significantly different major immune-related genes (IFNA, ISG15, and NFKB) compared to mock. Importantly, expression of the transcription factor FOXO1, which controls autophagy- and immune-related gene expression, was significantly lower at 30℃. Moreover, FOXO1 inhibition in temperature-optimized MDCK cells enhanced HuNoV replication, highlighting FOXO1 inhibition as an approach for successful virus replication. In the temperature-optimized cells, various HuNoV genotypes were successfully replicated, with GI.8 showing the highest replication levels followed by GII.1, GII.3, and GII.4. Furthermore, ultrastructural analysis of the infected cells revealed functional HuNoV replication at low temperature, with increased cellular apoptosis and decreased autophagic vacuoles. In conclusion, temperature-optimized MDCK cells can be used as a convenient culture model for HuNoV replication by inhibiting FOXO1 and providing adaptability to different genotypes.

• The Korean Journal of Physiology and Pharmacology
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• 제19권4호
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• pp.365-372
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• 2015

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor $(NF)-{\kappa}B$, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

• 한국식품영양과학회지
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• 제37권4호
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• pp.477-484
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• 2008

붕장어 가공부산물인 머리와 frame를 효율적으로 이용하기 위한 일련의 연구로 붕장어 부산물을 이용한 붕장어탕의 개발을 시도하였고, 아울러 이의 식품성분 특성에 대하여도 살펴보았다. 살균조건 및 가온일수에 따른 붕장어탕의 저장성 부여를 위한 최적 살균조건은 $F_0$ value=8분으로 판단되었다. 붕장어탕의 일반성분은 수분의 경우 90.7%, 조단백질의 경우 4.8%, 조지방의 경우 2.6%, 조회분의 경우 1.5%를 나타내었다. 붕장어탕의 엑스분 질소 함량은 243.1 mg/100g으로 시판 추어탕의 208.0 mg/100 g보다 높았다. 붕장어탕의 총 아미노산 함량은 4,310 mg/100 g이었고, 주요 구성아미노산은 glutamic acid(637.3 mg/100 g, 14.8%), glycine(409.1 mg/100 g, 9.5%) 및 alanine(404.4 mg/100 g, 9.3%)등이었다. 붕장어탕은 관능적인 비린내는 거의 감지되지 않았고, 맛은 우수하였으며, 항산화능이 인정되었으나 ACE 저해능은 크게 기대할 수 없었다.

• 동의생리병리학회지
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• 제20권6호
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• pp.1732-1741
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• 2006

Obesity is chronic disease which influenced on health severly. The causes of obesity have been known as life change, lack of excercise, genetic factor, mental and social economic factors. Especially the obesity of women increased the risk of the diseases such as DM, osteoarthritis, cardiovascular disease, breast cancer and infertility. The limitations of the widely used negative definition of health as the absence of disease and WHO's 1946 definition of health as total social, psychological and physical well-being have long been recognized (WHO 1958). The Quality of Life (QoL) includes functional ability, the degree and quality of social and community interaction, psychological well-being as somatic sensation and life satisfaction. I investigated to compare the differences between obese women (n=63), non-obese women (n=37) in clinic and general women (n=43, control) on baseline characteristics and WHO QoL-BREF. The purpose of this study is to assist the diagnosis and treatment of obesity. WHO QoL-BREF is self administered type which consisted of 26 questions. The prospective question is calculated with 5 scores by Likert's method. The results are as follows : The means of physical, psychological, social, overall and total scores of QoL were significant among BMI group (P<0.05). The score of control group (BMI < 25) was higher than other groups significantly (P<0.05). In multiple regression analysis, the variable of high school/below middle school was significant in environmental and overall domain of QoL scores (P<0.05). The variable of college/below middle school was significant in environmental, overall domain and total score of QoL scores (P<0.05). The variable of above university/below middle school was significant in physical health, environmental, overall domain and total score in QoL scores (P<0.05). The variable of Health perception (moderate/bad) was positively significant in physical health, environmental, overall domain and total score of QoL scores (P<0.05). The variable of Health perception (good/bed) was positively significant in physical health, environmental, social, overall domain and total score of QoL scores (P<0.05). The variable as BMI non-=obese women/control was negatively significant in social domain of QoL scores (P<0.05). Above the results, It suggests that the variable as BMI did't affect on the QoL in patients and control, but the variables as education and health perception affected on the QoL scores. Further study is required to conduct QoL differences between before and after treatment of obese patients.

• 한국해양바이오학회지
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• 제1권2호
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• pp.76-83
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• 2006

본 연구에서는 다양한 인체암세포의 증식에 미치는 등불가사리 메탄올 추출물(MEGF)의 영향을 조사하였다. MEGF는 처리 농도의존적으로 암세포의 형태적변이 및 증식억제가 효과를 보여주었으며, 특히 백혈병세포에서 가장 높은 감수성을 보여주었다. 따라서 백혈병세포의 증식억제 효과가 apoptosis 유발과 연관성이 있는지를 flow cytometry 분석 및 DAPI staining 법으로 조사한 결과, MEGF 처리에 의한 백혈병세포의 증식억제는 세포주기 교란과 무관한 apoptosis 유발에 의한 것임을 sub-G1기 세포의 빈도 증가 및 apoptotic body 형성의 증가 등으로 확인하였다. 또한 MEGF 처리에 의한 백혈병세포의 증식억제 및 apoptosis 유발은 p53 비의존적인 p21의 발현 증가 및 Fas/FasL system의 발현 증가와 연관성이 있음을 알 수 있었다. 이상의 결과들은 인체 암세포, 특히 백혈병세포에서 MEGF의 항암작용을 이해하는데 중요한 자료가 될 것이고 나아가 MEGF 내 함유된 생리활성 물질의 분리 및 항암적용 연구를 위한 중요한 기초 자료로 활용될 것이다.