• BMB Reports
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• 제52권9호
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• pp.548-553
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• 2019

Ets-1 is a prototype of the ETS protein family. Members of the ETS protein family contain a unique ETS domain. Ets-1 is associated with cancer progression and metastasis in many types of cancer. Many studies have shown a link between elevated expression of Ets-1 in cancer biopsies and poor survival. CCR7 is a chemokine that binds to specific ligand CCL21/CCL19. CCR7 expression is associated with tumor metastasis and infiltration into lymph nodes. The objective of this study was to test whether Ets-1 could regulate CCR7 expression and enhance tumor metastasis. Our data showed that CCR7 expression was downregulated in Ets-1-deficient T cells upon T-cell stimulation. Overexpression of Ets-1 increased CCR7 expression in breast cancer cell lines. In contrast, knockdown of Ets-1 reduced CCR7 expression. Ets-1 could directly bind to CCR7 promoter and mediate CCR7 expression in luciferase reporter assays and chromatin immunoprecipitation assays. Transactivation activity of Ets-1 was independent of the Pointed domain of Ets-1. Ets-1 could also enhance $NF-{\kappa}B$ and CBP transactivation of CCR7 promoter. Our results also showed that Ets-1 could modulate cancer cell transmigration by altering CCR7 expression in transwell assay and wound healing assay. Taken together, our data suggest that Ets-1 can enhance CCR7 expression and contribute to tumor cell migration.

• 대한수의학회지
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• 제59권2호
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• pp.59-67
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• 2019

We investigated whether ${\beta}$-carotene (${\beta}-CA$) or ellagic acid (EA), originating from various fruits and vegetables, has a preventive effect against male infertility induced by exogenous scrotal hyperthermia. ICR adult mice were intraperitoneally treated with 10 mg/kg of ${\beta}-CA$ or EA daily for 13 days consecutively. During this time, mice were subjected to transient scrotal heat stress in a water bath at $43^{\circ}C$ for 20 min on day 7, and their testes and blood were obtained on day 14 for histopathologic and biochemical analyses. Heat stress induced significant testicular weight reduction, germ cell loss and degeneration, as well as abnormal localization of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and manganese superoxide dismutase (MnSOD) in spermatogenic and Leydig cells. Heat stress also altered the levels of oxidative stress (lipid peroxidation, SOD activity, and PHGPx, MnSOD, and $HIF-1{\alpha}$ mRNAs), apoptosis (Bax, Bcl-xL, caspase 3, $NF-{\kappa}B$, and $TGF-{\beta}1$ mRNAs), and androgen biosynthesis (serological testosterone concentration and $3{\beta}$-hydroxysteroid dehydrogenase mRNA) in testes. These changes were all improved significantly by ${\beta}-CA$ treatment, but only slightly improved by EA treatment. These findings indicate that ${\beta}-CA$, through modulations of oxidative stress, apoptosis, and androgen biosynthesis, is a potent preventive agent against testicular injuries induced by scrotal hyperthermia.

• 대한본초학회지
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• 제32권2호
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• pp.65-75
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• 2017

Objectives : This study aimed to evaluate the protective effect of Orostachydis Herba (OH) and Fermented OH (OHF) against the acute liver injury by lipopolysaccharide (LPS). Methods : OHF by 4 lactic bacteria such as (Lactobacillus hilgardii (OHF1), Leuconostoc mesenteroides (OHF2), Pediococcus acidilactici (OHF3), Saccharomyces cerevisiae (OHF4)) were prepared. Samples were selected to OHF0, OHF2, OHF3 based on UPLC analysis, DPPH, ABTS radical scavenging activities. To evaluate the protective effect of OHF on liver injury mice, ICR mice were divided into 5 groups: Normal mice (Nor), LPS (20 mg/kg) treated mice (Veh), administrated OHF0, OHF2 OHF3 200 mg/kg body weight during 8 days before LPS injection. Serum and liver were collected 24 hours after LPS injection. Results : The activity was high in order of OHF0 and OHF3 in DPPH and ABTS radical scavenging activities. The quercetin contents for bioactive ingredient of OH was 5.39, kaempferol contents was 9.94 by UPLC analysis. The LPS-treated vehicle group significantly increased liver weight, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in serum. In contrast, administrated OHF3 group decreased liver weight, AST, ALT. In addition, OHF3 groups reduced the elevated levels of reactive oxygen species (ROS) in serum and tissues. Moreover, AP-1, iNOS and COX-2 were significantly decreased in OHF2 and OHF3. But $NF-{\kappa}B$ p65 and $TNF-{\alpha}$ only showed a significant reduction in OHF3. Conclusions : Therefore, these results suggest that fermented Orostachydis Herba might be protective effect on liver injury through anti-oxidant effect.

• 대한한의학회지
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• 제43권3호
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• pp.1-15
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• 2022

Objectives: Myrrh have been used as a traditional remedy to treat infectious and inflammatory diseases. However, it is largely unknown whether myrrh ethanol extract could exhibit the inhibitory activities against particulate matter (PM)-induced skin injury on human keratinocytes, HaCaT cells. Therefore, this study was aimed to investigate the inhibitory activity of myrrh ethanol extract on PM-induced skin injury in HaCaT cells. Methods: To investigate the inhibitory effects of myrrh ethanol extract in HaCaT cells, the skin injury model of HaCaT cells was established under PM treatment. HaCaT keratinocyte cells were pre-treated with myrrh ethanol extract for 1 h, and then stimulated with PM. Then, the cells were harvested to measure the cell viability, reactive oxygen species (ROS), pro-inflammatory cytokines including interleukin (IL) 1-beta, IL-6, and tumor necrosis factor (TNF)-𝛼, hyaluronidase, collagen, MMPs. In addition, we examined the mitogen activated protein kinases (MAPKs) and inhibitory kappa B alpha (I𝜅-B𝛼) as inhibitory mechanisms of myrrh ethanol extract. Results: The treatment of myrrh ethanol extract inhibited the PM-induced cell death and ROS production in HaCaT cells. In addition, myrrh ethanol extract treatment inhibited the PM-induced elevation of IL-1beta, IL-6, and TNF-𝛼. Also, myrrh ethanol extract treatment inhibited the increase of hyaluronidase, MMP and decrease of collagen. Furthermore, myrrh ethanol extract treatment inhibited the activation of MAPKs and the degradation of I𝜅-B𝛼. Conclusions: Our result suggest that treatment of myrrh ethanol extract could inhibit the PM-induced skin injury via deactivation of MAPKs and nuclear factor (NF)-𝜅B in HaCaT cells. This study could suggest that myrrh ethanol extract could be a beneficial agent to prevent skin damage or inflammation.

• 한방재활의학과학회지
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• 제32권4호
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• pp.9-18
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• 2022

Objectives This study was conducted to confirm the anti-inflammatory effect of Naetakbaekryeom-san (NTB), and whether it could be another treatment for inflammatory diseases. Methods The NTB water extract was extracted with hot water at 100℃ for 2 hours, concentrated at 80℃ under reduced pressure, and used. After 2 hours of pretreatment with NTB and positive control Bay11-7082, nitric oxide (NO), inducible NO synthase (iNOS), interleukin (IL)-6, IL-1𝛽, tumor necrosis factor alpha (TNF-𝛼) were measured in RAW264.7 cells activated with lipopolysaccharides (LPS) 500 ng/mL. After 2 hours of pretreatment with NTB, the anti-inflammatory effect of NTB was evaluated by measuring nuclear factor kappa-light-chain-enhancer of activated B cells (NF-𝜅B) in RAW264.7 cells and 293T cells activated with phorbol 12-myristate 13-acetic acid (PMA) 30 ng/mL. Results In RAW264.7 cells activated with LPS, NTB at concentrations of 0.1, 0.3, and 1.0 mg/mL showed no cytotoxicity, significantly inhibited NO production and inhibition of iNOS expression. TNF-𝛼 cytokine levels was not regulated, but NTB at each concentration inhibited the production of IL-1𝛽 and IL-6, and the effect was higher than that of the positive control Bay11-7082 (20 𝜇M). In PMA-activated RAW264.7 cells and 293T cells, each concentration of NBT decreased the NF-𝜅B transcriptional activity, with the greatest decrease at 1 mg/mL. Conclusions These results demonstrated the anti-inflammatory effect of NTB water extracts, but further studies such as comparison of anti-inflammatory effects and antioxidant effects by NTB component, comparison of effects according to extraction solvents, and clinical studies are needed.

• IMMUNE NETWORK
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• 제11권1호
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• pp.79-94
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• 2011

Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

• 생명과학회지
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• 제30권9호
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• pp.804-812
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• 2020

본 연구에서는 아메리카왕거저리에 대한 기능성 연구의 일환으로 아메리카왕거저리 유충의 유전체 분석을 통해 선별된 조포바신 1의 항균 및 항염증 활성을 확인하였다. 선행연구에서 RNA 시퀀싱을 통해 아메리카왕거저리의 전사체를 분석하였으며, 결과를 바탕으로 인실리코(in silico) 분석을 수행하여 전사체 유래 항균 펩타이드를 스크리닝하고 선발하였다. 수행된 항균활성 및 용혈활성 테스트에서 조포바신 1은 세균 및 칸디다 진균에 대해 광범위한 항균활성을 나타낸 반면 마우스 적혈구에 대한 용혈활성은 전혀 없었다. 다음으로 마우스 대식세포주 Raw264.7 세포를 이용하여 조포바신 1의 항염증활성을 확인하였다. 그 결과 조포바신 1은 LPS로부터 유도된 Raw264.7 세포들의 산화질소 생성을 감소시키는 결과를 보여주었다. 뿐만 아니라 실시간 역전사 중합효소 연쇄반응(qRT-PCR) 방법과 효소결합면역흡착측정법(ELISA)을 통해 조포바신 1이 Raw264.7 세포에서 전염증성 사이토카인(IL-6, IL-1β)의 발현을 감소시킨다는 것을 확인할 수 있었다. 또한 염증반응의 신호전달인자들(MAPKs, NF-κB)의 인산화를 억제하는 것을 확인하였다. 게다가 조포바신 1은 LPS와의 상호작용을 통해 결합한다는 것을 확인하였다. 이러한 연구결과들은 아메리카왕거저리 유전체 분석을 통해 확인된 조포바신 1이 항균 및 항염증 치료를 위한 물질로서 개발하는데 가능성이 있을 것으로 사료된다.

• 한국미생물·생명공학회지
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• 제42권2호
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• pp.170-176
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• 2014

본 연구에서는 Euptelea pleiosperma 에탄올 추출물(EPEE)의 항산화능과 항염증 생리활성을 in vitro assay system 및 cell culture model system을 이용하여 분석하였다. 먼저 EPEE의 항산화능을 DPPH radical scavenging activity로 분석한 결과 radical 소거능의 정도가 양성 대조군으로 사용한 ascorbic acid 보다 높은 활성을 보여 매우 강한 항산화능을 보유함을 확인하였다. 또한 RAW 264.7 세포주를 이용한 $H_2O_2$ 및 LPS의 유도에 의해 생성된 ROS에 대한 소거능을 분석한 결과에서도 농도의존적인 강한 소거능을 보였다. 뿐만 아니라 대표적인 항산화효소 중 하나로 천연물에 의한 항산화능 활성에 의해 주로 발현이 유도되는 hemeoxygenase 1 (HO-1) 및 그 전사 인자인 nuclear factor-E2-related factor 2 (Nrf2)의 단백질 발현이 EPEE의 처리에 의해 유의적으로 증가됨을 보였으며 이러한 HO-1 및 Nrf2의 발현 변화는 상위신호전달계인 MAPKs 및 PI3K/Akt 에 의해 조절될 가능성을 보였다. 한편 EPEE가 LPS에 의해 유도된 NO 생성에 미치는 영향을 분석한 결과 농도의존적인 NO 생성 저해능을 보였으며 이는 NO 생성 단백질인 iNOS의 발현 저해에서 기인함을 확인하였다. 이와 같은 EPEE의 NO 생성 억제 효과는 염증 상위신호전달계인 NF-${\kappa}B$ 및 AP-1의 조절을 통해 일어날 가능성을 보였다. 이러한 결과를 통해 EPEE의 높은 항산화능과 항염증 활성을 처음으로 확인하였으며 향후 기능성 소재로서 유용하게 활용될 수 있을 것으로 판단된다.

• 한국식품영양과학회지
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• 제45권6호
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• pp.911-917
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• 2016

본 연구에서는 야관문 에탄올 추출물의 인체 대장암세포 성장억제 효능 및 그 기전을 연구하였다. 야관문 에탄올 추출물을 0, 200, 400, $600{\mu}g/mL$ 농도로 48시간 처리하여 암세포 증식억제 효과를 측정한 결과 농도 의존적으로 감소하는 것으로 확인하였다. HT-29 세포에 대한 야관문 추출물의 $IC_{50}$ 값은 $554.26{\pm}8.81{\mu}g/mL$로 확인되었다. 또한 야관문 에탄올 추출물을 처리한 HT-29 세포에 대한 세포 성장 억제 기전을 확인한 결과 pro-caspase 3의 발현이 감소함에 따라 PARP의 분절 및 DNA 분절을 확인하고 anti-apoptotic단백질인 Bcl-2를 감소시켰으며 pro-apoptotic 단백질인 Bax의 수준을 증가시키는 것으로 확인하였다. 염증 관련 유전자 $TNF-{\alpha}$, IL-6 그리고 그의 전사인자인 $NF-{\kappa}B$는 야관문 에탄올 추출물 처리농도에 의존적으로 감소하는 것으로 확인하였고 유전자 SIRT1의 발현량도 증가하는 것으로 확인하였다. 그 결과 야관문 에탄올 추출물 처리에 따라서 HT-29의 세포 성장억제가 확인되어 apoptosis를 유도하는 것으로 확인되었고, 이러한 연구 결과는 야관문이 기능성 소재로서 기초적 데이터베이스로 활용될 수 있을 것으로 생각되며 앞으로 더욱더 야관문의 질병에 대한 효능 및 기전연구가 지속하여야 할 것으로 생각된다.

• Journal of Nutrition and Health
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• 제41권3호
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• pp.224-231
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• 2008

본 연구는 십자화과 채소의 섭취로 체내유용 물질인 인돌이 전립선암 세포 PC3 cell의 항전이 효과 기전에 미치는 영향에 대하여 알아보았다. 인돌은 전립선암 세포중식을 농도 의존적으로 억제하였으며 인돌에 의한 세포 사멸의 영향과 관계없이 MMP-2, -9의 활성과 전사수준 및 단백질 발현을 억제하였다. 역으로 MMP활성 억제 물질인 TIMP-1,-2의 발현이 인돌 첨가에 의해 증가하였다. $NF{-\kappa}B$의 upstream에 존재하는 MAPK signaling 유전자인 ERK1/2, p38, JNK 발현이 인돌처리로 인산화를 억제하였다. 그리고 전립선암 세포 PC3 침윤성이 인돌 처리 시 유의적으로 감소하였다. 결론적으로 인돌은 PC3 인체 전립선암 세포의 전이 과정을 MAPK phthway를 통한 MMP 활성과 발현 억제, TIMP 발현 증가로 암 세포 전이 억제를 하는 것 으로 나타나 암 전이 억제 식품으로 가능성을 제시한다.