• Title/Summary/Keyword: CCR1

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Overexpression of AtCAF1, CCR4-associated factor 1 homologue in Arabidopsis thaliana, negatively regulates wounding-mediated disease resistance

  • Kwon, Tack-Min;Yi, Young-Byung;Nam, Jae-Sung
    • Journal of Plant Biotechnology
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    • v.38 no.4
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    • pp.278-284
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    • 2011
  • The CCR4-CAF1-NOT complex-mediated degradation of mRNA is a fundamental aspect of gene regulation in eukaryotes. We herein examined the role of AtCAF1 in the innate immune and wound responses of plants. Our results showed that overexpression of AtCAF1 significantly downregulated the transcript level of EFR but not FLS2 and BRI1, as well as abolished up-regulated expression pattern of EFR in response to wounding. Consistently, Agrobacteriummediated transient expression of GUS was highly enhanced in the transgenic plants overexpressing AtCAF. Furthermore, JA responsive genes were down-regulated by overexpression of AtCAF, causing the transgenic plants overexpressing AtCAF more susceptible to necrotrophic fungal pathogen, Botrytis cinerea. These results suggest that The CCR4-CAF1-NOT complex-mediated degradation of mRNA negatively regulates wounding-mediated disease resistance in Arabidopsis thaliana.

No Association between the CCR5Δ32 Polymorphism and Sporadic Esophageal Cancer in Punjab, North-West India

  • Sambyal, Vasudha;Manjari, Mridu;Sudan, Meena;Uppal, Manjit Singh;Singh, Neeti Rajan;Singh, Harpreet;Guleria, Kamlesh
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4291-4295
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    • 2015
  • Background: Chemokines and their receptors influence carcinogenesis and cysteine-cysteine chemokine receptor 5 (CCR5) directs spread of cancer to other tissues. A 32 base pair deletion in the coding region of CCR5 that might alter the expression or function of the protein has been implicated in a variety of immune-mediated diseases. The action of antiviral drugs being proposed as adjuvant therapy in cancer is dependent on CCR5 wild type status. In the present study, distribution of CCR5${\Delta}32$ polymorphism was assessed in North Indian esophageal cancer patients to explore the potential of using chemokine receptors antagonists as adjuvant therapy. Materials and Methods: DNA samples of 175 sporadic esophageal cancer patients (69 males and 106 females) and 175 unrelated healthy control individuals (69 males and 106 females) were screened for the CCR5${\Delta}32$ polymorphism by direct polymerase chain reaction (PCR). Results: The frequencies of wild type homozygous (CCR5/CCR5), heterozygous (CCR5/${\Delta}32$) and homozygous mutant (${\Delta}32/{\Delta}32$) genotypes were 96.0 vs 97.72%, 4.0 vs 1.71% and 0 vs 0.57% in patients and controls respectively. There was no difference in the genotype and allele frequencies of CCR5${\Delta}32$ polymorphism in esophageal cancer patients and control group. Conclusions: The CCR5${\Delta}32$ polymorphism is not associated with esophageal cancer in North Indians. As the majority of patients express the wild type allele, there is potential of using antiviral drug therapy as adjuvant therapy.

Administrative Information Disclosure and Relative Efficiency Analysis for Universities or Colleges (대학의 행정정보공개와 상대적 효율성 분석)

  • Choi, Ho-Taek;Kang, Ho-Jung
    • The Journal of the Korea Contents Association
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    • v.10 no.11
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    • pp.371-379
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    • 2010
  • This study analyzes relative efficiency analysis for universities or colleges of Chung Cheong regions using data envelopment analysis. The main results of this study can by summarized as follows. First, in case of efficiency for CCR, the number of efficient universities(CCR value is one) are five universities. and mean value of CCR for universities located in Chungbuk region was most high. Second, the number of efficient colleges(CCR value is one) are three colleges. and mean value of CCR for colleges located in Daejeon region was most high. Third, in case of efficiency for BCC, the number of efficient universities(BCC value is one) are nine universities. and mean value of BCC for universities located in Chungbuk region was most high. Fourth, the number of efficient colleges(BCC value is one) are seven colleges. and mean value of BCC for colleges located in Chungbuk region was most high.

Investigation of the Binding Site of CCR2 using 4-Azetidinyl-1-aryl-cyclohexane Derivatives: A Membrane Modeling and Molecular Dynamics Study

  • Kothandan, Gugan;Gadhe, Changdev G.;Cho, Seung Joo
    • Bulletin of the Korean Chemical Society
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    • v.34 no.11
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    • pp.3429-3443
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    • 2013
  • Chemokine receptor (CCR2) is a G protein-coupled receptor that contains seven transmembrane helices. Recent pharmaceutical research has focused on the antagonism of CCR2 and candidate drugs are currently undergoing clinical studies for the treatment of diseases like arthritis, multiple sclerosis, and type 2 diabetes. In this study, we analyzed the time dependent behavior of CCR2 docked with a potent 4-azetidinyl-1-aryl-cyclohexane (4AAC) derivative using molecular dynamics simulations (MDS) for 20 nanoseconds (ns). Homology modeling of CCR2 was performed and the 4AAC derivative was docked into this binding site. The docked model of selected conformations was then utilized to study the dynamic behavior of the 4AAC enzyme complexes inside lipid membrane. MDS of CCR2-16b of 4AAC complexes allowed us to refine the system since binding of an inhibitor to a receptor is a dynamic process and identify stable structures and better binding modes. Structure activity relationships (SAR) for 4AAC derivatives were investigated and reasons for the activities were determined. Probable binding pose for some CCR2 antagonists were determined from the perspectives of binding site. Initial modeling showed that Tyr49, Trp98, Ser101, Glu291, and additional residues are crucial for 4AAC binding, but MDS analysis showed that Ser101 may not be vital. 4AAC moved away from Ser101 and the hydrogen bonding between 4AAC and Ser101 vanished. The results of this study provide useful information regarding the structure-based drug design of CCR2 antagonists and additionally suggest key residues for further study by mutagenesis.

CCR7 Ligands Induced Expansion of Memory CD4+ T Cells and Protection from Viral Infection (CCR7 Ligand의 Memory CD4+ T 세포 증가유도 및 바이러스 감염에 대한 방어효과)

  • Eo, Seong-Kug;Cho, Jeong-Gon
    • IMMUNE NETWORK
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    • v.3 no.1
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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.

HQSAR Analysis on Novel series of 1-(4-Phenylpiperazin-1-yl-2-(1H-Pyrazol-1-yl) Ethanone Derivatives Targeting CCR1

  • Balasubramanian, Pavithra K.;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.6 no.3
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    • pp.163-169
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    • 2013
  • The chemokine receptor CCR1 a GPCR super family protein contains seven transmembrane domains. It plays an important role in rheumatoid arthritis, organ transplant rejection, Alzheimer's disease and also causes inflammation. Because of its role in disease processes, antagonism of CCR1 became an attractive therapeutic target. In the current study, we have taken a novel series of recently reported CCR1 antagonist of 1-(4-Phenylpiperazin-1-yl_-2-(1H-Pyrazol-1-yl) ethanone derivatives and performed a HQSAR analysis. The model was developed with Atom (A) and bond (B) parameters and with different set of atom counts to improve the model. The results of HQSAR showed good predictive ability in terms of $r^2$ (0.904) and $q^2$ (0.590) with 0.710 as standard error of prediction and 0.344 as standard error of estimate. The contribution map depicted the atom contribution in inhibitory effect. Compound-14 which was reported to be a highly active compound showed positive atom contribution in three R groups ($R^3$. $R^{5a}$ and $R^{2b}$) in inhibitory effect, which could be the reason why this compound is highly active compound whereas, the lowest active compound-6 showed negative contribution to inhibitory effect.

Chemotactic Effect of Leukotactin-1/CCL15 on Human Neutrophils

  • Lee Ji-Sook;Yang Eun-Ju;Ryang Yong-Suk;Kim In-Sik
    • Biomedical Science Letters
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    • v.12 no.3
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    • pp.145-151
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    • 2006
  • Leukotactin-l (Lkn-l )/CCL15 has been known as a potent chemoattractant of leukocytes. However, the precise function of Lkn-l in human neutrophils has not been explained well. In the present study, we investigated the contribution of Lkn-1 in chemotactic activity of human neutrophils. Both CCR1 and CCR3 mRNA expressions are strongly expressed in human neutrophils but CCR2 protein expression was uniquely detected on the cell surface. Lkn-l binding to CCR1 and CCR3 induced chemotactic activity of neutrophils. Chemotactic index of Lkn-l was comparable to that of IL-8. $MIP-1{\alpha}/CCL3$ binding to CCR1 and CCR5 has no effect on neutrophil migration. Cell migration, in response to Lkn-l, was blocked by pertussis toxin (Ptx), a $G_o/G_i$ protein inhibitor, and U73122, a phospholipase C(PLC) inhibitor but not by protein kinase C inhibitor such as rottlerin, and Ro-31-8425. Taken together, our results demonstrate that Lkn-l transduces the chemotaxis signal through $G_o/G_i$ protein and PLC. This finding provides the molecular mechanism by which Lkn-l may contribute to neutrophil movement into the site of inflammation.

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A Study on Management Efficiency of Korean Ship Component Part Manufacturers

  • Kim, Myung-Jae
    • Journal of Navigation and Port Research
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    • v.34 no.7
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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.

CCR5-mediated Recruitment of NK Cells to the Kidney Is a Critical Step for Host Defense to Systemic Candida albicans Infection

  • Nu Z. N. Nguyen;Vuvi G. Tran;Saerom Lee;Minji Kim;Sang W. Kang;Juyang Kim;Hye J. Kim;Jong S. Lee;Hong R. Cho;Byungsuk Kwon
    • IMMUNE NETWORK
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    • v.20 no.6
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    • pp.49.1-49.15
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    • 2020
  • C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5-/- mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5-/- mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c+ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.

Improving Outcome of Mass Media (매스미디어 운영에 따른 성과제고에 관한 연구 -국내 신문산업을 중심으로-)

  • Hwang, Jong-Ho
    • The Journal of the Korea Contents Association
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    • v.13 no.1
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    • pp.366-375
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    • 2013
  • Recently, management of Newspaper developmet of the internet news, broadcasting and free newspapers escalated competition between newspaper companies and other media companies as well as competition among newapaper companies. This paper analyzes the efficiency of Korean Newapaper using DEA model. We evaluate the CCR-O, BCC-O efficiency, SE and RTS of 30 Newspaper. We also suggest the Newpaper which can be benchmarked based on analyzed information. The result shows that ten Nespaper whose values of CCR-O efficiency are 1, and Fourteen Nespaper whose values of BCC efficiency are 1. RTS indicates IRS of 1 firms, DRS of 16 firms and CRS of 13 firms. To variables on the effectiveness of newspaper publishing companies for the understanding and performance analysis.