• 제목/요약/키워드: CTL cell

검색결과 69건 처리시간 0.034초

CTL cell에서의 우세장 발생과 특성 (The generation and characteristics of the dominant field in CTL cell)

  • 박웅희
    • 한국정보통신학회논문지
    • /
    • 제17권5호
    • /
    • pp.1055-1063
    • /
    • 2013
  • 전자파 내성 및 전자파 장해 측정을 위한 표준 전자파 발생 장치 중 하나인 CTL cell에서 두 개의 입력 단자에 동일 신호와 역위상 신호 입력에 따른 다양한 전계와 자계 발생에 대해 살펴보았다. 기본 공진주파수 TE011이 2.20GHz인 CTL cell을 이용하여 우세 전계장과 우세 자계장 조건에서 입력 전력의 변화에 따른 전계 특성, 측정 위치에 따른 전계 특성, 주파수 변화에 따른 전계 특성을 측정하였고, 이를 이용하여 CTL cell의 측정 영역에서의 동작 특성과 공진주파수의 영향을 받지 않고 사용 가능한 주파수 대역을 살펴보았다.

항원수용체자극에 의한 Cytolytic T cell 특이전사체 표현유도 (Antigen Receptor-Mediated Induction of Cytolytic T cell-Specific Transcripts Expression)

  • 김관식;;권병세
    • 대한약리학회지
    • /
    • 제23권1호
    • /
    • pp.45-49
    • /
    • 1987
  • Cytolytic T cell(CTL)에서는 표현되나 다른 세포에서는 표현되지 않는 유전자를 검색하여 최근 저자는 3종의 CTL 특이 cDNA를 cloning하였다. CTL 특이 cDNA의 기능을 규명하기 위하여 CTL L3 cell을 항원수용체를 통하여 혹은 interleukin 2(IL-2)로 자극하여 활성화시킨 후 RNA blot analysis로 각 cDNA clone의 상응전사체 표현양상을 관찰, CTL활성화과정과의 연관성을 실험하였다. 이중 2종의 cDNA상응전사체표현은 항원수용체자극에 의해 현저히 증가된 반면 IL-2는 전혀 영향을 미치지 않았으며 이 같은 전사체표현증가는 cyclosporin A 처리로 완전히 억제되었다. 이상의 결과는 항원수용체자극으로 활성화되는 유전자가 IL-2에 의해 활성화되는 유전자와는 상이함을 보여주는 것이며 또한 2종의 cDNA clone이 IL-2에 의해 활성화되지 않으나 항원수용체를 통하여 중개되며 cyclosporin A에 예민하게 반응하는 CTL활성화과정의 특정경로에 관여하는 것으로 사료된다.

  • PDF

Molecular and Functional Characterization of Choline Transporter-Like Proteins in Esophageal Cancer Cells and Potential Therapeutic Targets

  • Nagashima, Fumiaki;Nishiyama, Ryohta;Iwao, Beniko;Kawai, Yuiko;Ishii, Chikanao;Yamanaka, Tsuyoshi;Uchino, Hiroyuki;Inazu, Masato
    • Biomolecules & Therapeutics
    • /
    • 제26권4호
    • /
    • pp.399-408
    • /
    • 2018
  • In this study, we examined the molecular and functional characterization of choline uptake in the human esophageal cancer cells. In addition, we examined the influence of various drugs on the transport of [$^3H$]choline, and explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. We found that both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were highly expressed in esophageal cancer cell lines (KYSE series). CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is both $Na^+$-independent and pH-dependent. Choline uptake and cell viability were inhibited by various cationic drugs. Furthermore, a correlation analysis of the potencies of 47 drugs for the inhibition of choline uptake and cell viability showed a strong correlation. Choline uptake inhibitors and choline deficiency each inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be involved in choline uptake in mitochondria, which is the rate-limiting step in S-adenosylmethionine (SAM) synthesis and DNA methylation. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for esophageal cancer therapy.

Functional Expression of Choline Transporter-Like Protein 1 in LNCaP Prostate Cancer Cells: A Novel Molecular Target

  • Saiki, Iwao;Yara, Miki;Yamanaka, Tsuyoshi;Uchino, Hiroyuki;Inazu, Masato
    • Biomolecules & Therapeutics
    • /
    • 제28권2호
    • /
    • pp.195-201
    • /
    • 2020
  • Prostate cancer is one of the most common cancers in men. Choline PET or PET/CT has been used to visualize prostate cancer, and high levels of choline accumulation have been observed in tumors. However, the uptake system for choline and the functional expression of choline transporters in prostate cancer are not completely understood. In this study, the molecular and functional aspects of choline uptake were investigated in the LNCaP prostate cancer cell line along with the correlations between choline uptake and cell viability in drug-treated cells. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed in LNCaP cells. CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. [3H]Choline uptake was mediated by a single Na+-independent, intermediate-affinity transport system in the LNCaP cells. The anticancer drugs, flutamide and bicalutamide, inhibited cell viability and [3H]choline uptake in a concentration-dependent manner. The correlations between the effects of these drugs on cell viability and [3H]choline uptake were significant. Caspase-3/7 activity was significantly increased by both flutamide and bicalutamide. Furthermore, these drugs decreased CTL1 expression in the prostate cancer cell line. These results suggest that CTL1 is functionally expressed in prostate cancer cells and are also involved in abnormal proliferation. Identification of this CTL1-mediated choline transport system in prostate cancer cells provides a potential new therapeutic target for the treatment of this disease.

골관절염 실험모델에서 꾸지뽕나무 추출물의 골관절염 억제효과 연구 (Therapeutic Effects of Curdrania tricuspidata Leaf Extract on Osteoarthritis)

  • 남다은;김옥경;이정민
    • 한국식품영양과학회지
    • /
    • 제42권5호
    • /
    • pp.697-704
    • /
    • 2013
  • 본 실험에서는 primary culture된 연골세포 in vitro 실험모델과 MIA로 유발한 골관절염 in vivo 실험모델을 이용하여 꾸지뽕나무 잎 추출물의 관절염 예방 효과를 확인하였다. 먼저 MTT 시험법을 통해 세포 사용 적정농도를 $500{\mu}g/mL$ 이하로 결정하여 연골세포사멸 억제를 확인하고, 이를 근간으로 골관절염 동물실험 모델에서 골관절염 예방효과를 확인하였다. $H_2O_2$ 처리에 따른 산화적 독성으로 연골세포 사멸을 유도한 실험에서 꾸지뽕 잎 추출물은 정상세포 수준으로 사멸을 억제하였으며, 이러한 효과는 CTL80의 $200{\mu}g/mL$, CTL10의 $300{\mu}g/mL$ 농도에서 비교적 높게 나타났다. 교원질 합성을 억제하고 분해를 촉진시키는 MMPs(MMP-7, MMP-13)의 발현을 실시간 정량 PCR로 측정하여 발현변화를 살펴보았다. 그 결과 앞선 세포실험 결과와 마찬가지로 CTL80과 CTL10 처리군에서 발현이 유의적으로 낮아졌음을 살펴볼 수 있었다. 특히 CTL80에서 MMP-7과 MMP-13의 발현이 농도 유의적으로 감소하였으며, CTL10의 경우 200, $300{\mu}g/mL$ 농도에서 유의적으로 발현이 감소하는 것을 확인하였다. 세포실험 결과를 바탕으로 동물실험에서의 적정농도를 결정하였으며, 동물독성실험 결과 이상이 없음을 확인하고 실험을 진행하였다. 이때 세포실험결과 선정된 두농도(200, $300{\mu}g/mL$) 간의 차이가 미미하여 동물실험에 적용할 경우 비슷한 실험결과가 나타날 것으로 사료되어 두 실험군 간의 결과를 정확히 구분 짓기 위해 200, $500{\mu}g/mL$ 농도를 선정하여 사용하였다. 골관절염 유발 동물모델을 만들기 위해 SD rat의 관절강에 MIA를 injection 하였으며, 꾸지뽕 잎 에탄올 추출물 투여에 따른 관절염 예방 효과를 관찰하기 위해 관절염 유발 2주일 전부터 1일 1회 경구투여를 실시하고, 유발 후 3주간 지속적으로 투여하고 관찰하였다. 동물 관절의 병리학적 변화를 관찰하기 위하여 Micro-CT 촬영 및 분석을 실시한 결과 Control 군은 골의 강도와 밀도가 감소한 반면, 양성대조군인 MTX 투여군에서 정상군과 비슷한 수준으로 회복된 것을 확인하였고, CTL80-200군과 CTL10-500군에서 Control 군에 비해 유의적으로 수치가 감소하여 골관절염에 따른 손상이 감소한 것을 확인하였다. 동물의 관절조직의 H&E 염색을 통한 조직학적인 변화에서는 골관절염 유발로 연골세포의 손상과 뼈조직의 손상을 관찰하였으며 관절형태를 알아볼 수 없을 정도로 손상된 것을 확인하였다. 반면 CTL80과 CTL10에서는 관절강 세포의 형태가 정상군과 비슷한 둥근모양을 띤 양상을 보였으며 연골조직의 형태가 잘 유지되어 Control 군에 비해 꾸지뽕잎의 투여효과가 나타났음을 관찰하였다. 이상의 결과를 통하여 꾸지뽕 잎 에탄올 추출물은 높은 항관절염 효과가 있을 것으로 사료되며, 항관절염 효능을 지니는 기능성 소재로써 개발 가능성을 확인하였다.

Molecular cloning and expression analysis of a C-type lectin in the rock bream, Oplegnathus fasciatus

  • Kwon, Mun-Gyeong;Kim, Ju-Won;Park, Myoung-Ae;Hwang, Jee-Youn;Park, Hyung-Jun;Park, Chan-Il
    • 한국어병학회지
    • /
    • 제25권1호
    • /
    • pp.11-20
    • /
    • 2012
  • C-type lectins are crucial for pathogen recognition, innate immunity, and cell-cell interactions. In this study, a C-type lectin gene was cloned from the rock bream. The full-length RbCTL cDNA was 729 bp with a 429 bp ORF encoding a 164-residue protein. The deduced amino acid sequence of RbCTL had all of the conserved features crucial for its fundamental structure, including the four cysteine residues involved in sulfide bridge formation and potential $Ca^2+$/carbohydrate-binding sites. RbCTL contains a signal peptide one single carbohydrate recognition domain. It showed 29.4% similarity to the C-type lectin of rainbow trout. RbCTL mRNA was predominately expressed in gill and head-kidney tissue and expressed less in peripheral blood leukocytes, trunk-kidney, spleen, liver, intestine and muscle. Expression of RbCTL was differentially upregulated in rock bream stimulated with LPS, Con A/PMA and poly I:C.

Chitinase 3-like-1, a novel regulator of Th1/CTL responses, as a therapeutic target for increasing anti-tumor immunity

  • Kim, Do-Hyun;Choi, Je-Min
    • BMB Reports
    • /
    • 제51권5호
    • /
    • pp.207-208
    • /
    • 2018
  • Chitinase-Like Proteins (CLPs) are an evolutionarily conserved protein which lose their enzymatic activity for degrading chitin macromolecules. Chitinase-3-like-1 (Chi3l1) is a type of CLP that is highly expressed in epithelial cells, macrophages, etc., and is known to have correlations with type 2 inflammation and cancer. Although the increased level of Chi3l1 in the blood was reported in various disease patients, the function of Chi3l1 in adaptive immunity has been totally unknown. Recently, we found that Chi3l1 is expressed in T cells and has a negative regulatory role in T-cell activation and proliferation. A genetic ablation study of Chi3l1 in T cells showed hyperresponsiveness to TcR stimulation, which increased proliferation and Th1 differentiation. A significant increase of $IFN{\gamma}$ signaling in Chi3l1-deficient T cells synergistically increased Th1 and CTL functions against melanoma cells in vitro and in vivo. In addition, targeted knockdown by Chi3l1 siRNA complexed with the cell-penetrating peptide dNP2, which showed decreased pulmonary melanoma metastasis with increased infiltration of Th1 and CTL in the lung. This study first suggests that Chi3l1 is a novel regulator of Th1/CTL responses and could be a target for treating cancer to increase tumor immunity.

Studies on Anti-inflammatory effect of Clerodendron trichotomum Thunberg Leaves

  • Choi, Jung-Ho;Whang, Wan-Kyun;Kim, Hong-Jin
    • 대한약학회:학술대회논문집
    • /
    • 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
    • /
    • pp.261.1-261.1
    • /
    • 2002
  • The leaves of Clerodendron trichotomum Thunberg(CTL) is used in Chinese folk medicine for anti-inflammatory properties. We studied on the anti-inflammatory effects of CTL extracts in rat. mouse and Raw 264.7cell. 1 mg/kg of 30%. 60% methanol fraction of CTL and 1 mg/kg of indomethacin as the standard anti-inflammatory drug were administrated into rats, respectively. Carrageenan was injected subcutaneously to induce hind paw edema in rats. (omitted)

  • PDF

Cytotoxic T Lymphocytes Elicited by Dendritic Cell-Targeted Delivery of Human Papillomavirus Type-16 E6/E7 Fusion Gene Exert Lethal Effects on CaSki Cells

  • Wu, Xiang-Mei;Liu, Xing;Jiao, Qing-Fang;Fu, Shao-Yue;Bu, You-Quan;Song, Fang-Zhou;Yi, Fa-Ping
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제15권6호
    • /
    • pp.2447-2451
    • /
    • 2014
  • Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer. Consideration of safety and non human leukocyte antigen restriction, protein vaccine has become the most likely form of HPV therapeutic vaccine, although none have so far been reported as effective. Since tumor cells consistently express the two proteins E6 and E7, most therapeutic vaccines target one or both of them. In this study, we fabricated DC vaccines by transducing replication-defective recombinant adenoviruses expressing E6/E7 fusion gene of HPV-16, to investigate the lethal effects of specific cytotoxic T lymphocytes (CTL) against CaSki cells in vitro. Mouse immature dendritic cells (DC) were generated from bone marrow, and transfected with pAd-E6/E7 to prepare a DC vaccine and to induce specific CTL. The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods. Immature mouse DC was successfully transfected by pAd-E6/E7 in vitro, and the transfecting efficiency was 40%-50%. A DC vaccine was successfully prepared and was used to induce specific CTL. Experimental results showed that the percentage of apoptosis and killing rate of CaSki cells were significantly increased by coculturing with the specific CTL (p <0.05). These results illustrated that a DC vaccine modified by HPV-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer.

Inhibition of Human $CD8^+$ Cytotoxic T Lymphocyte (CTL) -mediated Cytotoxicity in Porcine Fetal Fibroblast Cells by Overexpression of Human Cytomegalovirus Glycoprotein Unique Short (US) 2 Gene

  • Park, K-W.;Yoo, J.Y.;Choi, K.M.;Yang, B.S.;Im, G.S.;Seol, J.G.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • 제22권1호
    • /
    • pp.20-25
    • /
    • 2009
  • Xenotransplantation of pig organs into humans is a potential solution for the shortage of donor organs for transplantation. However, multiple immune barriers preclude its clinical application. In particular, the initial type of rejection in xenotransplantation is an acute cellular rejection by host $CD8^+$ cytotoxic T lymphocyte (CTL) cells that react to donor major histocompatibility complex (MHC) class I. The human cytomegalovirus (HCMV) glycoprotein Unique Short (US) 2 specifically targets MHC class I heavy chains to relocate them from the endoplasmic reticulum (ER) membrane to the cytosol, where they are degraded by the proteasome. In this study we transfected the US2 gene into minipig fetal fibroblasts and established four US2 clonal cell lines. The integration of US2 into transgenic fetal cells was confirmed using PCR and Southern blot assay. The reduction of Swine Leukocyte Antigen (SLA)-I by US2 was also detected using Flow cytometry assay (FACS). The FACS analysis of the US2 clonal cell lines demonstrated a substantial reduction in SLA-I surface expression. The level (44% to 76%) of SLA-I expression in US2 clonal cell lines was decreased relative to the control. In cytotoxicity assay the rate of $CD8^+$ T cell-mediated cytotoxicity was significantly reduced to 23.8${\pm}$15.1% compared to the control (59.8${\pm}$8.4%, p<0.05). In conclusion, US2 can directly protect against $CD8^+$-mediated cell lysis. These results indicate that the expression of US2 in pig cells may provide a new approach to overcome the CTL-mediated immune rejection in xenotransplantation.