• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.10
• /
• pp.4291-4295
• /
• 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.

• IMMUNE NETWORK
• /
• v.2 no.2
• /
• pp.86-90
• /
• 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.

• The Plant Pathology Journal
• /
• v.23 no.2
• /
• pp.109-112
• /
• 2007

This study was to examine the efficacy of a root-dipping application of antagonistic bacterial strains for the control of Phytophthora blight of pepper caused by P. capcisi, and to evaluate their plant growth-promoting effects in the field in 2005 and 2006. The candidate antagonistic rhizobacterial strains CCR04, CCR80, GSE09, ISE13, and ISE14 were treated by dipping plant roots with bacterial suspensions prior to transplanting. The candidate rhizobacterial strains CCR04, CCR80, GSE09, and ISE14 significantly (P=0.05) reduced the disease incidence and the area under the disease progress curves when compared to buffer-treated controls in at least a year test. The metalaxy l(fungicide-treated control) resulted in one of the lowest disease incidences among the treatments in both years. Moreover, the strains CCR04, CCR80, GSE09, and ISE13 significantly (P=0.05) increased the fruit weights and/or numbers of peppers in at least a year test compared to the buffer-treated controls. These results suggest that the antagonistic rhizobacterial strains CCR04, CCR80, and GSE09 could be efficient biocontrol agents by controlling Phytophthora blight of pepper and promoting the plant growth when treated with root-dipping at transplanting.

• IMMUNE NETWORK
• /
• v.3 no.1
• /
• pp.29-37
• /
• 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.

• International Journal of Oral Biology
• /
• v.44 no.4
• /
• pp.173-181
• /
• 2019

The CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor that regulates chemotaxis and effector functions of immune cells. It also serves as the major co-receptor for the entry of human immunodeficiency virus (HIV). Recently, CCR5 inhibitors have been developed and used for the treatment or prevention of HIV infections. Additionally, it has been identified that CCR5 controls bone homeostasis by regulating osteoclastogenesis and the communication between osteoblasts and osteoclasts. However, the effects of CCR5 inhibition on bone tissue in elderly patients are unknown. This study aimed to examine the bone phenotype of aged CCR5 knockout (KO) mice. Femoral and tibial bones were isolated from 12-month and 18-month old wild-type (WT) and CCR5 KO mice, and microcomputed tomography and histology analyses were performed. Twelve-month-old CCR5 KO mice exhibited a decreased trabecular bone mass and cortical bone thickness in both femoral and tibial bones compared with age-matched WT mice. Eighteen-month-old mice also showed a decreased trabecular bone mass in femurs compared with control WT mice, but not in tibial bones. Unlike in 12-month-old mice, the cortical margin of femurs and tibias in 18-month-old mice were rough, likely because they were aggravated by the deficiency of CCR5. Overall, our data suggest that the deficiency of CCR5 with aging can cause severe bone loss. When CCR5 inhibitors or CCR5 inactivating technologies are used in elderly patients, a preventive strategy for bone loss should be considered.

• Journal of Life Science
• /
• v.13 no.4
• /
• pp.541-550
• /
• 2003

E2 glycoprotein of hepatitis C virus (HCV) comprises a surface of viral particle together with E1 glycoprotein, and is thought to be involved in the attachment of HCV viral particle to receptor (s) on the permissible cells including hepatocytes, B cells, T cells, and monocytes. We constructed a phage library expressing cellular proteins of hepatocytes on the phage surface, which turned out to be 8.8${\times}$$10^5$ cfu of diversity and carried inserts in 95% of library. We screened both cDNA phage library and 12-mer peptide library to identify the cellular proteins binding to E2 protein. Some intracellular proteins including tensin and membrane band 4.1 which are involved in signal transduction of survival and cytoskeleton organization, were selected from cDNA phage library through several rounds of panning and screening. On the contrary, membrane proteins such as CCR7, CKR-L2, and insulin-like growth factor-1 receptor were identified through screening of peptide library. Phages expressing peptides corresponding to those membrane proteins were bound to E2 protein specifically as determined by neutralization of binding assay. Since it is well known that HCV can infect T cells as well as hepatocytes, we examined to see if E2 protein can bind to CCR7, a member of C-protein coupled receptor family expressed on T cells, using CCR7 transfected tells. Human CCR7 cDNA was cloned into pcDNA3.1(-) vector and transfected into human embryonic kidney cell, 293T, and expressed on the surface of the cell as shown by flow cytometer. Binding assay of E2 protein using CCR7 transfected cells indicated that E2 protein bound to CCR7 by dose-dependent mode, giving rise to the possibility that CCR7 might be a putative cellular receptor for HCV.

• Biomedical Science Letters
• /
• v.18 no.4
• /
• pp.435-437
• /
• 2012

House dust mite (HDM) is important in the pathogenesis of allergic diseases including asthma and atopic dermatitis. Dermatophagoides pteronissinus (Dp) is one of major HDM allergens. In this study, we investigated that Dp extract (DpE) affects on the chemotactic activity of monocytes isolated from the peripheral blood. DpE inhibited the migration of human monocytes in response to CC chemokines such as MIP-$1{\alpha}$, RANTES, HCC-4, MCP-1, and TARC. DpE did not alter the expression of CC chemokine receptors (CCRs) such as CCR1, CCR2, CCR3, CCR4, and CCR5. These results indicate that DpE blocks the chemotaxis of human monocytes and its mechanism is not involved in alteration of CCR expression. Better understanding of the effect of DpE on monocytes will enable elucidation of the role of Dp in the development of allergic diseases.

• Journal of Integrative Natural Science
• /
• v.7 no.4
• /
• pp.234-240
• /
• 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.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.11
• /
• pp.3429-3443
• /
• 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.

• The korean journal of orthodontics
• /
• v.40 no.5
• /
• pp.325-333
• /
• 2010

Objective: The aim of this study was to illustrate the circumferential comfortable retainer (CCR) as a removable maxillary retainer with good potential patient compliance and to evaluate the discomfort of the retainers including distorted speech, gagging sensation and appliance discomfort. Methods: Sixty-six orthodontic patients (male, 23; female, 43; mean age, $23.42{\pm}10.19$ years) who received orthodontic treatment with fixed orthodontic appliances were randomly assigned to two groups after debonding, a conventional wraparound retainer (CWR) group that fully covers the palate with an acrylic plate and a highly polished surface, and a circumferential comfortable retainer (CCR) group which has a horseshoe shaped base plate with three folds on the anterior region. A questionnaire that had a visual analog scale (VAS) which consists of a 100-mm horizontal line with 2 end-points labeled "no discomfort" on the left and "worst discomfort" on the right, with regard to distorted speech, gagging sensation and discomfort, was administered to patients after 4 weeks of retainer wear. The Mann-Whitney test was used to test the hypothesis that there was no difference between the two retainers. Results: Comparing distorted speech and discomfort, the CCR group significantly had lower values than the CWR group ($p$ < 0.05). Comparing gagging sensation, the CCR group had lower values than the CWR group but there were no statistically significant differences between groups ($p$ = 0.146). Conclusions: In conclusion, the results suggest that the circumferential comfortable retainer (CCR) might facilitate patient compliance and thereby improve the maintenance of the fixed orthodontic treatment outcome.