• Journal of Pharmaceutical Investigation
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• v.33 no.4
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• pp.281-286
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• 2003

To design gene deliver systems which can deliver higher amounts of genes into stem cells, we studied the expression of receptors involved in the receptor-mediated endocytosis of bone marrow stromal stem cells. Bone marrow was isolated from ICR mice, and bone marrow stromal stem cells were isolated based on their plastic adherence property. Several culture conditions were screened for effective and continuous culture of marrow stromal stem cells. MesenCult medium was finally used to cultivate marrow stromal stem cells in vitro. As candidate receptors, various chemokine receptors were studied. Both bone marrow cells ad marrow-derived stromal stem cells showed expression of CC chemokine receptors (CCR) and CXC chemokine receptors (CXCR). Marrow stromal stem cells showed higher expression of CCR5 ad CXCR4 chemokine receptors as compared to other types of chemokine receptors. Moreover, though the expression of chemokine receptors generally decreased in most chemokine receptors with the cultivaton of marrow stromal stem cells, CCR5 and CXCR4 chemokine receptors retained the higher level of receptor expressions over prolonged periods. These results suggest that the ligands exhibiting specific binding to CCR5 or CXCR4 might be used to modify gene delivery systems for increased levels of receptor-mediated gene delivery into stromal stem cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4643-4646
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• 2016

The CC chemokine receptor 5 (CCR5) delta 32 allele results in a nonfunctional form of the chemokine receptor and has been implicated in a variety of immune-mediated diseases. $CCR5{\Delta}32$ may also predispose one to chronic liver disease or be linked with resistance to HBV infection. This study was undertaken to investigate any association between CCR5 polymorphism with resistance to hepatitis B or susceptibility to HBV infection. A total of 812 Iranian individuals were enrolled into two groups: HBV infected cases (n=357), who were HBsAg-positive, and healthy controls (n=455). We assessed polymorphisms in the CCR5 gene using specific CCR5 oligonucleotide primers surrounding the breakpoint deletion. Genotype distributions of the HBV infected cases and healthy controls were determined and compared. The CCR5/CCR5 (WW) and $CCR5/CCR5{\Delta}32$ (W/D) genotypes were found in (98%) and (2%) of HBV infected cases, respectively. The $CCR5{\Delta}32/{\Delta}32$genotype was not found in HBV infected cases. Genotype distributions of CCR5 in healthy controls were W/W genotype in (87.3%), W/D genotype in (11.2%) and D/D genotype in (1.5%). Heterozygosity for $CCR5/CCR5{\Delta}32$ (W/D) in healthy controls was greater than in HBV infected cases (11.2% vs 2%, p < 0.001). W/D and D/D genotypes were more prominent in healthy controls than in HBV infected cases. This study provides evidence that the $CCR5{\Delta}32$ polymorphism may have a protective effect in resistance to HBV infection at least in the Iranian population.

• Journal of the Korean Magnetic Resonance Society
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• v.9 no.2
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• pp.74-92
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• 2005

The high resolution solution structure of MCP-3 was determined using multinuclear, multidimensional NMR spectroscopy with an expressed and $^{13}C-\;and\;^{15}N-labeled$ protein. The MCP-3 has a typical chemokine fold including 3 anti-parallel $\beta-sheets$, and a C-terminal helix, but it exists as a monomer in solution under the conditions where the structure was determined (2 mM, pH 5.1 at $30^{\circ}C$). Based on the structure and the amino acid sequence compared to other chemokines we propose that Ile20 and Leu25 in MCP-3 play key roles in the formation of N-loop (residues between the $2^{nd}$ cysteine and the I sheet) which has been implicated as a determinant of chemokine specificity. Additional receptor binding surface is supplied by the 40s loop (residues between the 2 and the 3 sheet) and the binding interface of the acidic N-terminal region of chemokine receptor to MCP-3 would resemble the dimerization interface of CC type dimer.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.11
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• pp.1721-1728
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• 2018

Objective: The use of genetic markers can help to enhance reproduction in cattle, which is a very important trait for profitability in dairy production systems. This study evaluated the association between genotypes of leptin (LEP), toll-like receptor 4 (TLR4), and chemokine receptor of interleukin 8 C-X-C motif (CXCR1) genes and fertility traits in Czech Fleckvieh cattle. Methods: Phenotypic data from 786 Czech Fleckvieh cows raised on 5 farms in the Czech Republic were used, along with information from the 1st three parities. To determine genotype, the polymerase chain reaction-restriction fragment length polymorphism method was used. Results: Except for LEP g.-963C>T, all studied genotype frequencies of single nucleotide polymorphisms (SNPs) were distributed according to the Hardy-Weinberg equilibrium. Two LEP SNPs (g.-963C>T and c.357C>T) were associated with the age at the 1st calving, days open (DO), pregnancy rate after 1st service (PR), and calving interval (CLI). In LEP g.-963C>T the TT genotype heifers firstly calved 24 days earlier than CC genotype and the CT genotype cow showed a tendency for shorter DO and higher PR. In LEP c.357C>T we observed longer CLI and DO period in TT cows. In general, we can propose the TT genotype of g.-963C>T as favorable and the TT genotype of c.357C>T as unfavorable for a cow's fertility. Heterozygotes in TLR4 c.-226C>G were significantly associated with shorter CLI, and presented a nonsignificant tendency to be associated with higher PR. In CXCR1 c.777 C>G, we did not observe any relationship of this SNP with reproduction. Conclusion: Overall, the results showed that LEP could be an effective marker for improving reproduction in Czech Fleckvieh cattle. This study also provides novel insights into the relationship between TLR4 and CXCR1 SNPs and reproduction in dual-purpose cattle.

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