• 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.

• IMMUNE NETWORK
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• 제3권1호
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• pp.29-37
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• 2003

Background: CC chemokine receptor (CCR) 7 and cognate CCR7 ligands, CCL21 (formerly secondary lymphoid tissue chemokine [SLC]) and CCL19 (formerly Epstein-Barr virus-induced molecule 1 ligand chemokine [ELC]), were known to establish microenvironment for the initiation of immune responses in secondary lymphoid tissue. As described previously, coadministration of DNA vaccine with CCR7 ligand-encoding plasmid DNA elicited enhanced humoral and cellular immunity via increasing the number of dendritic cells (DC) in secondary lymphoid tissue. The author hypothesized here that CCR7 ligand DNA could effectively expand memory CD4+ T cells to protect from viral infection likely via increasing DC number. Methods: To evaluate the effect of CCR7 ligand DNA on the expansion of memory CD4+ T cells, DO11.10.BALB/c transgenic (Tg)-mice, which have highly frequent ovalbumin $(OVA)_{323-339}$ peptide-specific CD4+ T cells, were used. Tg-mice were previously injected with CCR7 ligand DNA, then immunized with $OVA_{323-339}$ peptide plus complete Freund's adjuvant. Subsequently, memory CD4+ T cells in peripheral blood lymphocytes (PBL) were analyzed by FACS analysis for memory phenotype ($CD44^{high}$ and CD62 $L^{low}$) at memory stage. Memory CD4+ T cells recruited into inflammatory site induced with OVA-expressing virus were also analyzed. Finally, the protective efficacy against viral infection was evaluated. Results: CCR7 ligand DNA-treated Tg-mice showed more expanded $CD44^{high}$ memory CD4+ T cells in PBL than control vector-treated animals. The increased number of memory CD4+ T cells recruited into inflammatory site was also observed in CCR7 ligand DNA-treated Tg-mice. Such effectively expanded memory CD4+ T cell population increased the protective immunity against virulent viral infection. Conclusion: These results document that CCR7 and its cognate ligands play an important role in intracellular infection through establishing optimal memory T cell. Moreover, CCR7 ligand could be useful as modulator in DNA vaccination against viral infection as well as cancer.

• 생명과학회지
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• 제13권4호
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• pp.541-550
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• 2003

본 실험에서는 C형 간염바이러스 (HCV)의 외피 단백질인 E2 당단백질에 결합하는 세포단백질들을 클로닝하기 위해 간세포 cDNA를 phage 표면에 발현시킨 phage library를 제작하였고, 12-mer peptide library와 함께 E2 단백질에 대해 panning을 실시하였다. 검색결과 세포내 신호전달과 cytoskeleton 구성에 관여하는 tensin, membrane protein band 4.1 등 세포질내 단백질과 CCR7, CKR-L2, insulin-like growth factor-1 receptor 등 세포막 단백질 등이 확인되었다. 이들 단백질들을 발현하는 phage들은 수용성 E2단백질을 이용한 결합중화반응 결과 E2 단백질에 특이적으로 결합함이 확인되었다. 사람 T 세포에서 주로 발현되는 CCR7 유전자를 PHA로 활성화된 사람 T 세포의 total RNA를 이용하여 증폭하고 클로닝하였다. 293T 세포에 transfection시켜 단백질 발현양상을 flow cytometer로 분석하여 70% 이상의 세포들이 CCR7을 발현하고 있음을 관찰하였다. 수용성 E2 단백질을 CCR7이 transfection된 세포와 mock transfection된 대조군 세포에 각각 반응시킨 결과 dose-dependent 양상으로 CCR7에 결합하였다.

• 통합자연과학논문집
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• 제7권4호
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• pp.234-240
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• 2014

C-C chemokine receptor type 4 (CCR4) is a chemokine receptor with seven transmembrane helices and it belongs to the GPCR family. It plays an important role in asthma, lung disease, atopic dermatitis, allergic bronchopulmonary aspergillosis, cancer, inflammatory bowel disease, the mosquito-borne tropical diseases, such as dengue fever and allergic rhinitis. Because of its role in wide spectrum of disease processes, CCR4 is considered to be an important drug target. Three dimensional structure of the protein is essential to determine the functions. In the present study homology modeling of human CCR4 was performed based on crystal structure of CCR5 chemokine receptor. The generated models were validated using various parameters. Among the generated homology models the best one is selected based on validation result. The model can be used for performing further docking studies to identifying the critical interacting residues.

• IMMUNE NETWORK
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• 제20권3호
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• pp.20.1-20.15
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• 2020

Memory CD8+ T cells in the immune system are responsible for the removal of external Ags for a long period of time to protect against re-infection. Naïve to memory CD8+ T cell differentiation and memory CD8+ T cell maintenance require many different factors including local environmental factors. Thus, it has been suggested that the migration of memory CD8+ T cells into specific microenvironments alters their longevity and functions. In this review, we have summarized the subsets of memory CD8+ T cells based on their migratory capacities and described the niche hypothesis for their survival. In addition, the basic roles of CCR7 in conjunction with the migration of memory CD8+ T cells and recent understandings of their survival niches have been introduced. Finally, the applications of altering CCR7 signaling have been discussed.

• IMMUNE NETWORK
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• 제2권2호
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• pp.86-90
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• 2002

Background: Host genetic polymorphisms in the HIV-1 co-receptor CCR5 and CCR2b and SDF-1, ligand for co-receptor CXCR4, have been known to be associated with the resistance of HIV infection and/or the delayed disease progression in HIV-infected patients. Methods: We examined the frequencies of SDF1-3'A and CCR2b-64I alleles of 354 Koreans including 100 HIV-uninfected persons, 13 discordant spouses of HIV-infected persons, and 241 HIV-infected persons. The genotyping assays of SDF1 and CCR2b genes were carried out by polymerase chain reaction-restriction fragment length polymorphism. Results: The frequencies of CCR2b-64I and SDF1-3'A alleles in Koreans were very high compared with Caucasians and blacks. Observed frequencies of CCR2b-64I and SDF1-3'A allelic variants were 25.1% and 28.7%, respectively. The frequency of the CCR2b-64I allele in Koreans was 2~4 times higher than those of other ethnic groups with the exception of Asian. The frequencies of CCR2b-64I and SDF1-3'A genotypes did not show the significant difference between HIV-infected and uninfected Koreans. However, the prevalence of CCR2b-64I genotype of the LTNP group was about two times higher than that of the remainder group (P< 0.05). Four (45%) out of 9 LTNPs (long-term nonprogressors) showed having the SDF1-3'A allele and 7 (78%) out of 9 LTNPs carried the CCR2b-64I allele. 3 (33%) out of 9 LTNPs had both SDF1-3'A and CCR2b-64I alleles. But none of 5 RPs (rapid progressors) appeared to have both SDF1-3'A and CCR2b-64I alleles. Conclusion: The different genetic backgrounds in study populations may affect the disease progression and the AIDS epidemic in each country. Further studies need to define whether high frequencies of CCR2b-64I and SDF1-3'A allelic variants may affect the HIV disease progression.

• 한국항해항만학회지
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• 제34권7호
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• pp.577-585
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• 2010

This paper analyzes the efficiency of Korean Ship Component Part Manufacturer firms using DEA model. We evaluated the CCR, BCC efficiency and RTS of 30 Korea Ship Component Part Manufacturer firms. We also suggested the Korean Ship Component Part Manufacturer firms that can be benchmarked based on analyzed information. The result showed five enterprises whose values of CCR efficiency are 1, and eleven enterprises whose values of BCC efficiency are 1. RTS indicated IRS of 1 firms, DRS of 24 firms and CRS of 5 firms.

• Journal of Yeungnam Medical Science
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• 제41권2호
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• pp.103-112
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• 2024

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods: Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW 264.7 cells. Results: DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8⁺ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

• 한국콘텐츠학회논문지
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• 제12권7호
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• pp.284-294
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• 2012

본 연구는 전국지방의료원연합회에서 발간하고 있는 경영평가통계편람에서 2005년부터 2009년까지 지방의료원의 운영실적자료를 이용하여 DEA의 CCR 모형, AP모형, superSBM 모형의 각 효율성을 측정하여 비교 분석하였다. 그리고 환경요인(지역, 종별형태, 운영형태, 교육수련여부, 수요와 공급여건, 의료급여 환자비율)별 superSBM 모형의 효율성의 차이를 확인하기 위하여 Willcoxon- Mann- Whitney 통계량을 이용하여 분석하였다. 분석결과, 첫째, SuperSBM 모형에서 15%~17.1%, CCR 모형에서 13%~15.5%, AP 모형에서 7%~12.6%의 비효율을 보여 주고 있다. 둘째, 지역, 병원종별 형태, 병원운영형태, 수요와 공급여건, 저소득층의 진료비 비중 등 환경적 요인에 따라 효율성의 차이가 발생하였다. 셋째, 환경요인에 의해 발생되는 비효율을 해소하기 위해서는 병원내부의 독자적인 노력만으로 한계가 있으며 정부와 지방자치단체의 정책과 제도의 개선이 뒷받침되어야 한다.

• 한국콘텐츠학회논문지
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• 제8권7호
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• pp.201-207
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• 2008

현재 아파트 건설 산업의 경쟁적인 사업 환경으로 인해 아파트 건설기업의 파산 가능성은 더욱 높아졌다. 본 연구의 목적은 아파트 건설기업(상장기업)의 매출액과 당기순이익에 따른 효율성을 DEA분석기법으로 분석하는 것으로써 벤치마킹의 대상이 될 수 있는 아파트 건설기업의 효율성을 분석하였다. 총 25개 아파트 건설기업들의 CCR, BCC 효율성과 규모수익성(RTS)을 평가하였다. 또한 분석된 자료를 바탕으로 벤치마킹의 대상이 될 수 있는 아파트 건설기업을 제시하였다. 분석결과 CCR효율성이 1인 업체는 4개 기업, BCC효율성이 1인 업체는 10개 기업으로 분석되었다. 규모수익성은 IRS가 21개의 기업, CRS가 4개의 기업으로 분석되었다.