A functional interaction between the CCR5 and CD34 molecules expressed in hematopoietic cells can support (or even promote) the development of cancer

Abstract Inflammation and angiogenesis are linked to the development of cancer since both can support the establishment of a tumor-prone microenvironment. The CCR5 is a major regulatory molecule involved in inflammation. The CD34 molecule is commonly described as a hematopoietic stem cell marker, and CD34+ cells are involved in the regulation of distinct physiological processes, including angiogenesis. CCR5 participates in the development of various types of cancer, and recently, a reduced CCR5 expression was associated with low CD34+ cell counts in human cord blood. A naturally occurring genetic variant of the CCR5 gene, the so-called CCR5Δ32 polymorphism, consists of a 32 base-pair deletion in the DNA, interfering in the CCR5 protein levels on the cell surface. When in homozygosis, this variant leads to a total absence of CCR5 expression on the cell surface. In heterozygous individuals, CCR5 surface levels are reduced. Based on these key findings, we hypothesize that a functional interaction can connect CCR5 and CD34 molecules (giving rise to a "CCR5-CD34 axis"). According to this, a CCR5-CD34 interaction can potentially support the development of different types of cancer. Consequently, the lack of CCR5 in association with reduced CD34+ cell counts could indicate a protective factor against the development of cancer. It is required to characterize in detail the functional relationship between CCR5 and CD34 proteins, as well as the real influence of both molecules on the susceptibility and development of cancer at population level. If our hypothesis is confirmed, the CCR5-CD34 axis may be a potential target in the development of anti-cancer therapies.

Effects of antagonistic peptide specifically binding to second extracellular loop of CCR5 on inflammatory cell infiltration and TNF-α expression in lung tissues of asthmatic mice induced by OVA / 中国病理生理杂志

AIM: To investigate the effects of antagonistic peptide specifically binding to the second extracellular loop of CC chemokine receptor 5 (CCR5) on inflammatory cell infiltration and TNF-α expression in lung tissues of asthmatic mice.METHODS: The asthmatic model of BALB/c mice was induced by ovalbumin (OVA) and the optimal sensitization concentration of OVA was screened.After modeling, the mice were intervened by gradual concentrations of antagonistic peptide via tail-vein injection.The pathocytological analysis and grading were performed in the lung tissues with HE staining.The expression of TNF-α at mRNA and protein levels in the lung tissues was determined by real-time PCR and Western blot.RESULTS: The optimal concentration of OVA was 500 mg/L (0.1 mL) as this concentration of OVA stably induced moderate degree of inflammation in the BALB/c mice.Treatment with different concentrations (1.5 g/L, 2.5 g/L and 3.5 g/L) of antagonistic peptide at 0.2 mL through tail-vein injection inhibited the expression of TNF-α, and markedly reduced the degree of inflammation in the lung tissues.The optimal concentration of antagonistic peptide was 2.5 g/L as the lung inflammation degree in 2.5 g/L group alleviated by 2 grades, and the number of inflammatory cells was also significantly reduced.Moreover, the mRNA expression abundance of TNF-α was nearly decreased by 90%, and the protein expression of TNF-α was decreased by 70% compared with model group.Meanwhile, the use of antagonistic peptide at 2.5 g/L before OVA stimulation confirmed the preventive function to some degree.In this group, the lung inflammation degree alleviated by 1 grade, and the expression of TNF-α at both mRNA and protein levels decreased by nearly 50%.CONCLUSION: The antagonistic peptide of CCR5 effectively inhibits the expression of TNF-α and relieves the inflammation in the asthmatic mouse lung tissues in a concentration-dependent manner.

Panning and identification of antagonistic active peptides specifically bin-ding to the first and second extracellular membrane loops of rat CCR5 by technique of phage display peptide library / 中国病理生理杂志

[ ABSTRACT] AIM: To pan the active peptides which specifically bound to the first and second extracellular membrane loops of rat CC chemokine receptor 5 ( CCR5 ) .METHODS: The technique of phage display peptide library was used and binding ability of the peptides was identified.The amino acid sequences of the first and second extracellular loops of rat CCR5 were searched in the protein database and chemically synthesized corresponding linear peptides were used as targets in the biopanning.After 3 to 4 rounds of screening with Ph.D.TM-7 Phage Display Peptide Library were per-formed, the specific phages were collected and primarily identified by ELISA.RESULTS:The sequences of the peptides displayed on the selected phages were GHWKVWL and HYIDFRW, both of them exhibited positive in phage binding ELISA and the binding to phages and targets were concentration dependent and saturable.CONCLUSION:Two antagonis-tic active peptides specifically binding to CCR5 were successfully obtained by the technique of phage display peptide librar-y, and the binding ability to the first and second extracellular membrane loops of rat CCR5 were proved in vitro.

Toll like receptor 2 and CC chemokine receptor 5 cluster in the lipid raft enhances the susceptibility of Leishmania donovani infection in macrophages.

In experimental visceral leishmaniasis the causative obligate protozoan parasite, L. donovani invades and multiplies inside of macrophages, one of the sentries of the mammalian immune system. The initial host-parasite interaction between the Leishmania promastigote and the macrophage takes place at the plasma membrane interface. To trace any possible interaction between Toll-like receptor 2 (TLR2) and CC chemokine receptor 5 (CCR5) during early Leishmania-macrophage interactions, it was observed that the expression of both TLR2 and CCR5 were significantly increased, along with their recruitment to the lipid raft. TLR2 silencing attenuates CCR5 expression and restricts L. donovani infection, indicating a regulatory role of TLR2 and CCR5 during infection. Silencing of CCR5 and TLR2 markedly reduced the number of intracellular parasites in macrophages by host protective cytokine responses, while raft disruption using β-MCD affected TLR2/CCR5 cross-talk and resulted in a significant reduction in parasite invasion. In vivo RNA interference of TLR2 and CCR5 using shRNA plasmids rendered protection in Leishmania donovani-infected mice. Thus, this study for the first time demonstrates the importance of TLR2/CCR5 crosstalk as a significant determinant of Leishmania donovani entry in host macrophages.

Distribution of CC-chemokine receptor-5-32 allele among the tribal and caste population of Vidarbha region of Maharashtra state.

BACKGROUND: Genetic relationships among the ethnic groups are not uniform across the geographical region. Considering this assumption, we analyzed the frequency of the CC-chemokine receptor-5 (CCR5)-32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in Bhil tribal and Brahmin caste sample sets from the population. MATERIALS AND METHODS: 108 blood samples were collected from 6 tribe's populations and a caste population from the district of Vidarbha region. RESULTS AND DISCUSSION: The presence of low frequencies of CCR5-Δ32 in an individual of Bhil tribe (0.034, χ2 value 0.017) in the present study implies that these communities may have a better resistance toward human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) than the other studied tribe sample, as non-show such mutation. CONCLUSION: The marginal presence of the allele seen in the studied tribal population could be due to gene flow from the people of European descent. However, lack of the homozygous CCR5-Δ32 mutation and the low prevalence of heterozygous CCR5-Δ32 mutations suggest that the Indians are highly susceptible to HIV/AIDS, and this correlates with the highest number of HIV/AIDS infected individuals in India.

Expression of chemokine receptor CCR5 in human follicular thyroid carcinoma / 第二军医大学学报

Objective: To study the expression of chemokine receptor CCR5 in follicular thyroid carcinoma and the serum level of CCR5 ligand, so as to assess the role of CCR5 in progression and metastasis of follicular thyroid carcinoma. Methods: Fifteen samples of follicular thyroid carcinoma, 17 samples of follicular thyroid adenoma and 12 adjacent normal samples were analyzed immunohistochemically for CCR5 expression. The sera concentrations of CCL3, CCL4 and CCL5 were measured by ELISA in all patients. Results: CCR5 was positive in follicular thyroid carcinoma samples, with the positive rate being 73.33%, and was not detected in the follicular thyroid adenoma and the normal samples (P<0.01). The concentrations of CCL3 and CCL5 in the sera of follicular thyroid carcinoma patients were significantly higher than those of the other 2 groups (P<0.05). Conclusion: CCR5 is highly expressed in follicular thyroid carcinoma tissues and the concentrations of CCL3 and CCL5 are obviously increased in the sera of patients, indicating that CCR5 may play an important role in the pathogenesis of follicular thyroid carcinoma.

Expression of chemokine receptor CCR5 in human follicular thyroid carcinoma / 第二军医大学学报

Objective:To study the expression of chemokine receptor CCR5 in follicular thyroid carcinoma and the serum level of CCR5 ligand,so as to assess the role of CCR5 in progression and metastasis of follicular thyroid carcinoma.Methods:Fifteen samples of follicular thyroid carcinoma,17 samples of follicular thyroid adenoma and 12 adjacent normal samples were analyzed immunohistochemically for CCR5 expression.The sera concentrations of CCL3,CCL4 and CCL5 were measured by ELISA in all patients.Results:CCR5 was positive in follicular thyroid carcinoma samples,with the positive rate being 73.33%,and was not detected in the follicular thyroid adenoma and the normal samples(P

Blocking the CC chemokine receptor 5 pathway by antisense peptide nucleic acid prolongs islet allograft survival / 中国普通外科杂志

Objective To identify the effect of peptide nucleic acid of CC chemokine receptor 5 on acute rejection of islet allograft.Methods Mice islet transplant models were used to test the effect of PNA CCR5 by targeting CCR5 in acute allograft rejection.In vitro T cell proliferative responses were assessed by mixed lymphocyte response(MLR).RT-PCR and Western blot were used to detect the expression of mRNA and protein.Results PNA CCR5-treated recipients demonstrated statistically significant prolongation(12.00?1.75)d in functional allograft survival when compared with saline(6.50?0.58)d or PNA mismatch-treated recipients(6.50?0.50)d.The CCR5 mRNA expression level of PNA CCR5,control,and PNA mismatch treatment recipients at day 7 posttransplant was 0.56?0.05,1.68?0.07 and 1.80?0.14,respectively.The data showed that CCR5 protein was significantly down-regulated in PNA CCR5 treatment allografts compared with saline and PNA mismatch treatment allografts(P

Expression of chemokine receptor CCR5 in human invasive ductal breast carcinoma / 第二军医大学学报

Objective:To detect the expression of chemokine receptor CCR5 in human invasive ductal breast carcinoma and explore the role of CCR5 in breast cancer.Methods: Thirty samples of invasive ductal breast carcinoma and 10 samples of breast fibroadenoma were analyzed separately by immunohistochemical staining for CCR5 expression. MIP1?,MIP1? and RANTES concentrations were measured by ELISA in the sera of patients. Results: The expression of CCR5 was detected in invasive ductal breast carcinoma (the positive rate was 53.3%) and was not detected in breast fibroadenoma. RANTES concentrations in the serum of breast carcinoma patients increased significantly (P