• 제목/요약/키워드: production-inducing effect

검색결과 194건 처리시간 0.028초

In vitro Activation of Procaspase-8 by Forming the Cytoplasmic Component of the Death-inducing Signaling Complex (cDISC)

  • Roy, Ankoor;Hong, Jong hui;Lee, Jin-Hee;Lee, Young-Tae;Lee, Bong-Jin;Kim, Key-Sun
    • Molecules and Cells
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    • 제26권2호
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    • pp.165-170
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    • 2008
  • Procaspase-8 is activated by forming a death-inducing signaling complex (DISC) with the Fas-associated death domain (FADD) and the Fas receptor, but the mechanism of its activation is not well understood. Procaspase-8 devoid of the death effector domain at its N-terminus (${\Delta}nprocaspase-8$) was reported to be activated by kosmotropic salts, but it has not been induced to form a DISC in vitro because it cannot interact with FADD. Here, we report the production of full-length procaspase-8 and show that it is activated by adding the Fas death domain (Fas-DD) and the FADD forming the cytoplasmic part of the DISC (cDISC). Furthermore, mutations known to affect DISC formation in vivo were shown to have the same effect on procaspase-8 activation in vitro. An antibody that induces Fas-DD association enhanced procaspase-8 activation, suggesting that the Fas ligand is not required for low-level activation of procaspase-8, but that Fas receptor clustering is needed for high-level activation of procaspase-8 leading to cell death. In vitro activation of procaspase-8 by forming a cDISC will be invaluable for investigating activation of ligand-mediated apoptosis and the numerous interactions affecting procaspase-8 activation.

Immunomodulatory Activity of Ginsan, a Polysaccharide of Panax Ginseng, on Dendritic Cells

  • Kim, Mi-Hyoung;Byon, Yun-Young;Ko, Eun-Ju;Song, Jie-Young;Yun, Yeon-Sook;Shin, Taek-Yun;Joo, Hong-Gu
    • The Korean Journal of Physiology and Pharmacology
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    • 제13권3호
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    • pp.169-173
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    • 2009
  • Ginsan, a Panax ginseng polysaccharide that contains glucopyranoside and fructofuranoside, has immunomodulatory effects. Although several biologic studies of ginsan have been performed, its effects on dendritic cells (DCs), which are antigen-presenting cells of the immune system, have not been studied. We investigated the immunomodulatory effects of ginsan on DCs. Ginsan had little effect on DC viability, even when used at high concentrations. Ginsan markedly increased the levels of production by DCs of IL-12 and TNF-${\alpha}$, as measured by ELISA. To examine the maturation-inducing activity of ginsan, we measured the surface expression levels of the maturation markers MHC class II and CD86 (B7.2) on DCs. It is interesting that ginsan profoundly enhanced the expression of CD86 on DC surfaces, whereas it increased that of MHC class II only marginally. In $^3H$-thymidine incorporation assays, ginsan-treated DCs stimulated significantly higher proliferation of allogeneic $CD4^+$ T lymphocytes than did medium-treated DCs. Taken together, our data demonstrate that ginsan stimulates DCs by inducing maturation. Because DCs are critical antigen-presenting cells in immune responses, this study provides valuable information on the activities of ginsan.

Oleanolic acid 3-acetate, a minor element of ginsenosides, induces apoptotic cell death in ovarian carcinoma and endometrial carcinoma cells via the involvement of a reactive oxygen species-independent mitochondrial pathway

  • Jo, Hantae;Oh, Jeong-Hyun;Park, Dong-Wook;Lee, Changho;Min, Churl K.
    • Journal of Ginseng Research
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    • 제44권1호
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    • pp.96-104
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    • 2020
  • Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (∆Ψm), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ∆Ψm, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate-induced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

봉독요법(蜂毒療法)의 항염증(抗炎症) 기전(機轉) 연구(硏究)에 관(關)한 고찰(考察) (The Review on the Study related to Anti-inflammatory Mechanism of Bee Venom Therapy)

  • 최정식;박장우;오민석
    • 혜화의학회지
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    • 제15권1호
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    • pp.141-160
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    • 2006
  • The obtained results are summarized as follows 1. New findings are reporting year by year as for the study related to Anti-inflammatory mechanism of Bee Venom therapy. 2. The Anti-inflammatory effect of Bee Venom therapy is achieved through counterirritation, stimulations to adrenal cortex, immuno-regulation, antioxidation, removal of free radicals, modulation of AGP gene induction. 3. The chief components of Bee Venom related to Anti-inflammatory effect are Melittin, MCD peptide, Apamin, Adolapin etc. 4. Melittin binds to secretory phospholipase A2 and inhibits its enzymatic activity. 5. Melittin blocks neutophil O2-production. 6. MCD peptide(Peptide 401) stimulates the mast cell secrets histamine, Anti-inflammatory effect caused by this is 'conterirritation'. 7. Melittin & Apamin have an anti-inflammatory effect by inducing cortisone secretion. 8. MCD peptide & Apamin increase immunologic fuction by stimulating hypophysis & adrenal cortex and have an anti-inflammatory effect by inhibiting synthesis of prostaglandin from arachidonic acid. 9. Adolapin have an anti-inflammatory effect by inhibiting COX. 10. Bee Venom have an anti-inflammatory effect by suppressing AGP($\alpha$-acid glycoprotein). 11. Bee Venom have an anti-inflammatory effect by inhibiting NO, iNOS, PLA2, COX-2, TNF-$\alpha$, IL-1, NF-${\kappa}B$, MAP kinase.

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I-O모형을 이용한 부산 U-방재 실현의 경제적 파급 효과 분석에 관한 연구 (A Study on the Ripple Effect Economy of Busan Ubiquitous-Safety Realization on Using an Input-Output Model)

  • 류태창;김태민;김경수
    • 한국방재학회 논문집
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    • 제8권6호
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    • pp.93-100
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    • 2008
  • 부산은 해안과 접해 있는 지형적 특성과 인구집중에 따른 과밀, 고층건축물의 신축, 높은 건축밀도에 따라 자연재난(태풍, 해일, 홍수, 폭풍 지진 등) 인적재난(화재, 붕괴, 폭발 교통사고 등)의 발생규모 및 피해 정도가 날로 증가하고 있다. 이를 해결하기 위하여 부산시에는 2007년 부산 Ubiquitous-Safety Busan 모델 전략 및 설계를 통해 2020년을 목표로 Ubiquitous-Safety 실현하여 시민들의 재산과 생명을 보호할 수 있는 안전 시스템을 구축하기 위한 기본계획을 수립하였다. 이에 본 연구에서는 부산지역의 Ubiquitous-Safety 실현을 통해 지역 경제에 미치는 파급효과를 정량적으로 분석하였다. Ubiquitous-Safety 실현에 따른 부산지역의 생산유발파급효과는 약 2,500억의 직 간접효과가 발생할 것으로 예측되었다. 또한 부가가치유발효과 는 약 1,155억원의 직 간접효과가 발생한 것으로 예측되었고, 고용유발효과는 약 5,580명의 직럭 Ac 고용 파급효과가 창출될 것으로 예측되었으며 소득유발효과는 약 518억의 직 간접적인 부가가치 파급효과가 발생한 것으로 예측되었다. 부산 Ubiquitous-Safety 실현에 따른 지역경제 파급 분석에 관한 연구이다.

제주항 재개발사업의 경제적 가치 및 지역경제 파급효과 분석 (Analysis of Economic Value and Regional Economic Impact of Jeju Port Redevelopment Project)

  • 심기섭
    • 한국항만경제학회지
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    • 제38권3호
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    • pp.53-68
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    • 2022
  • 본 연구에서는 제주내항 재개발사업에 따른 경제적 가치와 경제적 파급효과를 추정하였다. 경제적 가치는 어메니티(Amenity)관점에서 경관개선, 환경개선, 레크레이션효과 등 비시장재화의 가치를 추정하였다. 추정결과, 모집단은 제주도와 기타지역으로 구분하여 개인의 지불의사금액을 조사한 결과, 제주도는 2,952.9원, 기타지역은 4,722.8원으로 추정되었다. 한편, 제주내항 재개발사업에 따른 경제적 파급효과는 사업기간중과 사업완료 이후의 경제적 파급효과를 추정하였다. 추정결과, 사업중에는 생산유발가치는 84,387백만원, 부가가치 유발효과는 37,292백만원, 고용유발가치는 (직접고용+간접고용)효과를 합치면 5,846명으로 나타났다. 사업기간 종료이후에는 2022년 기준으로 외국인 관광객 518천명이고, 부가가치 유발효과는 약 149,885백만원으로 추정되었다.

Effects of Oral Administration of Phellinus linteus on the Productions of the Th1- and Th2-type Cytokines in Mice

  • Oh, Gi-Su;Pae, Hyun-Ock;Choi, Byung-Min;Kwon, Ji-Wung;Yun, Yeong-Ho;Choi, Jeong-Ho;Kwon, Tae-Oh;Park, Young-Chul;Chung, Hun-Teag
    • IMMUNE NETWORK
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    • 제3권3호
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    • pp.182-187
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    • 2003
  • Background: The mushroom Phellinus linteus (PL) has been shown to have the anti-tumor and immunostimulatory effects. We hypothesized that the hot water extract of PL (WEPL) exerts its significant immunostimulatory effect by inducing production of the Th1-derived cytokine interferon-${\gamma}$ (IFN-${\gamma}$) by T lymphocytes. Methods: T lymphocytes were isolated from the mice fed with 200 mg/kg of WEPL once a day for 4 weeks, and then stimulated with the mitogen concanavaline A (Con A). IFN-${\gamma}$ gene and intracellular protein expressions were analyzed by RT-PCR and flow cytometry, respectively. The production of IFN-${\gamma}$ was measured by enzyme-linked immunosorbent assay. Results: WEPL significantly enhanced the transcription of IFN-${\gamma}$ mRNA. The effect of WEPL on IFN-${\gamma}$ expression was further supported by a concomitant increase in the number of cells with intracellular IFN-${\gamma}$ protein as well as the secretion of IFN-${\gamma}$. However, WEPL did not modulate either gene expression or protein secretion of interleukin-4, a Th2-associated cytokine, by Con A-stimulated T lymphocytes. Conclusion: Our results demonstrate that one of the potentially beneficial anti-tumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-${\gamma}$ secretion by T lymphocytes.

Prostaglandin Affects In Vitro Ovulation and 17α, 20β-Dihydroxy-4-pregnen-3-one Production in Longchin Goby, Chasmichthys dolichognathus Oocytes

  • Baek, Hea Ja;Lee, Da Som
    • 한국발생생물학회지:발생과생식
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    • 제23권2호
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    • pp.111-117
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    • 2019
  • This study focused on the association of prostaglandins and a progestin, $17{\alpha}$, $20{\beta}P$-dihydroxy-4-pregnen-3-one ($17{\alpha}20{\beta}P$) during the ovulation process in longchin goby, Chasmichthys dolichognathus. We performed several in vitro experiments using $850-920{\mu}m$ diameter oocytes which were at the migratory nucleus stage. With the $890-920{\mu}m$ diameter oocytes, no significant difference in ovulation was observed in any of the prostaglandins (PGE1, PGE2, and $PGF2{\alpha}$) treated groups although PGE2 and $PGF2{\alpha}$ at concentrations of 50 ng/mL increased ovulation slightly compared with controls; however, $17{\alpha}20{\beta}P$ production was stimulated with PGE1 alone at low concentrations (5 ng/mL). In $850{\mu}m$ diameter oocytes, $PGF2{\alpha}$ at concentrations of 50 and 500 ng/mL resulted in a significant increase in ovulation. $17{\alpha}20{\beta}P$ (50 ng/mL) alone had no observable effect on ovulation, but in the combined of $PGF2{\alpha}$ 50 or 500 ng/mL it caused the greatest effect on ovulation. The sensitivity of oocytes to the induction of ovulation varies between 850 and $890-920{\mu}m$, it appeared to vary depending on the migration status of nucleus. These results suggest that $PGF2{\alpha}$ (or combined of $17{\alpha}20{\beta}P$) was more potent in inducing ovulation of the longchin goby.

대식세포에서 Nrf2/HO-1경로를 통한 청심연자음의 항산화효과 (Anti-oxidative Effect of Chungsimyeonja-um (CSYJE) via Nrf2/HO-1 Pathway Activity in Lipopolysaccharide (LPS) Induced RAW 264.7 Macrophages)

  • 전선홍;오솔라;김소정;전보희;성진영;김용민
    • 대한화장품학회지
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    • 제46권3호
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    • pp.253-263
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    • 2020
  • 활성산소종(reactive oxygen species, ROS)은 우리 몸의 항상성 유지에 있어 중요한 역할을 한다. 그러나 과도한 ROS의 생성은 단백질, 지질, 핵산과 같은 세포 구성성분을 손상시키고 피부노화를 촉진시킨다. 이에 본 연구에서는 과도한 산화 스트레스를 예방하기 위해 Chungsimyeonja-um (CSYJE)의 항산화 효과를 확인하였다. 먼저 DPPH 및 ABTS assay를 실시하여 CSYJE의 항산화 효과를 확인한 결과 농도 의존적으로 radical 소거 활성을 확인하였다. 세포생존율 확인을 위해 MTT assay를 실시한 결과 1,000 ㎍/mL 농도에서 세포 독성이 없음을 확인하였다. 항산화 관련 단백질인 nuclear-E2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1)의 발현 수준을 확인하기 위해 western blotting을 실시한 결과 농도 의존적으로 발현이 증가하는 것을 확인하였다. 세포 내 ROS유발 물질인 lipopolysaccharide (LPS)로 ROS를 유도한 후, ROS생성 억제효과를 확인하기 위해 DCF-DA 염색법을 실시한 결과 농도 의존적으로 ROS 생성 억제효과를 확인하였으며 ROS의 생성으로 인한 염증성 사이토카인과 염증인자의 mRNA발현 수준을 확인하기 위해 real-time RT-PCR을 실시한 결과 농도 의존적으로 염증성 사이토카인과 염증인자의 mRNA 발현을 억제시켰다. 따라서, 본 연구는 Nrf2/HO-1 신호 전달 경로 활성을 통해 CSYJE의 항산화효과를 확인했으며 이는 CSYJE가 활성산소를 억제하여 항산화 화장품의 재료로서 사용될 수 있음을 시사한다.

Modulation of Aqueous Extracted Angelicae sinensis Radix on Nitric Oxide Production and Pro-inflammatory Cytokine Gene Expressions in RAW 264.7 Macrophage Cells

  • Lee Young Sun;Han Ok Kyung;Shin Sang Woo;Park Jong Hyun;Kwon Young Kyu
    • 동의생리병리학회지
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    • 제17권6호
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    • pp.1514-1518
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    • 2003
  • Angelica sinensis radix, Danggui, is a traditional oriental medication, which has been used to modulate immune response. We report here that aqueous extract of Angelica sinensis radix (ASR) can induces NO production, and inhibit LPS-induced NO production in dose-dependent manner in RAW 264.7 macrophage cells. ASR also induces iNOS mRNA and iNOS protein expression, and exhibit inhibitory effect on iNOS mRNA and protein expression in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophage cells. Cytokines involved in the regulation of inflammatory reaction and immune response may play a role in the pathogenesis. ASR induces. pro-inflammatory cytokine gene expression (IL-1α, IL-1β and IL-6 gene) in a dose-dependent manner, and inhibits the expressions of these cytokines in LPS-stimulated RAW 264.7 macrophage cells. These data indicate that (1) ASR may be a potential therapeutic modulator of NO synthesis in various pathological conditions, and (2) the immunomodulatory effects of ASR may be, in part, associated with the inducing or suppression of pro-inflammatory cytokine gene expressions.