Disease relevance of Ccr5

• Human CC chemokine receptor 5 (CCR5), a member of the superfamily of G protein-coupled receptors, regulates the activation and directed migration of leukocytes and serves as the main coreceptor for the entry of R5 tropic strains of human immunodeficiency viruses [1].
• Sequence analysis and infectious recombinant viruses containing peripheral nerve-derived C2V3 sequences indicated a predominance of CCR5-dependent and macrophage-tropic HIV-1, although dual tropic viruses using both CCR5 and CXCR4 were identified [2].
• Excitotoxic brain injury stimulates expression of the chemokine receptor CCR5 in neonatal rats [3].
• CONCLUSION: These data show that the CCR-5 chemokine receptor antagonist AOP-RANTES ameliorates M/M infiltration and improves glomerular pathology in experimental glomerulonephritis [4].
• In rat experimental autoimmune uveitis (EAU) we observed differential therapeutic effects of Met-RANTES, a CCR1/CCR5 receptor antagonist, depending on the retinal antigen peptides inducing the disease and the time of application during the afferent or efferent immune response [5].

Psychiatry related information on Ccr5

• The present study suggests that DAPTA and other CCR5 antagonists may attenuate critical aspects of the neuroinflammation associated with Alzheimer's disease [6].

High impact information on Ccr5

• We found no evidence for CCR5 association with caveolae during agonist-induced internalization [7].
• Using CCR5-transfected cell lines, immunofluorescence, and electron microscopy, we demonstrate that CCL5 causes the rapid redistribution of scattered cell surface CCR5 into large clusters that are associated with flat clathrin lattices [7].
• Receptors internalized via clathrin-coated vesicles follow the clathrin-mediated endocytic pathway, and depletion of clathrin with small interfering RNAs inhibits CCL5-induced CCR5 internalization [7].
• However, sequestration of cholesterol with filipin interferes with agonist binding to CCR5, suggesting that cholesterol and/or lipid raft domains play some role in the events required for CCR5 activation before internalization [7].
• Additionally, increases in tyrosine phosphorylation of CCR1 (days 14, 18, 21, and 24), CCR2 (days 14 and 18), and CCR5 (days 14, 18, and 21) were detected in AIA rats compared with control (nonarthritic) rats [8].

Biological context of Ccr5

• CONCLUSIONS: Given the association of chemokine receptors with progression to diabetes, it appears that interleukin-1beta-induced down-regulation of CCR3 and CCR5 promotes a protective mechanism against cellular destruction [9].
• The association of STAT-1 and STAT-3 with CCR5 on days 18 and 21 correlated with JAK-1 phosphorylation and binding on day 18 [8].
• Reverse transcription polymerase chain reaction revealed an increase in hippocampal CCR5 mRNA expression 24 hours after lesioning, and in situ hybridization analysis demonstrated that CCR5 mRNA was expressed in the lesioned hippocampus and adjacent regions [3].
• CCR1 and/or CCR5 blockade may have inhibitory effects on different phases of the autoimmune response, depending on the antigen specificity of T cells in EAU [5].
• Chemokine receptor 5 (CCR5) up-regulation may influence the recruitment and accumulation of glia near senile plaques; activated microglia express CCR5 and reactive astrocytes express chemokines [6].

Anatomical context of Ccr5

• While the majority of the CCR5 and p-STAT-1 immunostaining was on synovial lining cells and macrophages, p-STAT-3 was predominantly expressed on endothelial cells [8].
• CCR1, CCR2, and CCR5 tyrosine phosphorylation are associated with the JAK/STAT-1/STAT-3 pathway at different stages of rat AIA, as well as with macrophage and endothelial cell infiltration [8].
• CCR2 and CCR5 expression was detected in rat spleen, lung, kidney, thymus and macrophages; CCR5 mRNA was also detected in rat brain [10].
• Administration on days 7 through 14 after trinitrobenzene sulfonic acid administration of a CCR1/CCR5 receptor antagonist, Met-RANTES, resulted in a significant reduction of both macroscopic and microscopic colonic damage, as well as reducing the recruitment into the colon of monocytes, mast cells, and neutrophils [11].
• Some chemokines are up-regulated in pathological conditions of the central nervous system, and recently several chemokine receptors, including CCR5, were identified in the brain [3].

Associations of Ccr5 with chemical compounds

• CONCLUSION: CCR1, CCR2, and CCR5 mRNA expression and tyrosine phosphorylation increased with peak inflammation in the AIA model [8].
• We evaluated the impact of intrahippocampal injections of NMDA on CCR5 expression in postnatal day 7 rats [3].
• The well-established kainic acid seizure model was used in this study, focusing on the expression of the CCR5 chemokine receptor [12].
• Moreover, CCR5 mRNA ISH combined with neuron-specific enolase immunocytochemistry showed that, in addition to its glial expression, CCR5 mRNA is expressed in neurons in the normal brain and, to a lesser extent, after kainate treatment due to neuronal losses [12].

Other interactions of Ccr5

• RESULTS: Interleukin-1beta down-regulates constitutively expressed surface CCR3 and CCR5 levels implying receptor internalization for re-utilization or destruction, secretion or both [9].
• BACKGROUND: This study was designed to evaluate the role of the novel chemokine receptor antagonist amino-oxypentane RANTES (AOP-RANTES), which blocks the binding of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and RANTES to the chemokine receptor-5 (CCR-5) on the infiltration of monocytes in experimental glomerulonephritis [4].

Analytical, diagnostic and therapeutic context of Ccr5

• DESIGN AND MAIN OUTCOME MEASURES: The presence of membrane and cytoplasmic levels of CCR3 and CCR5 expression is assessed by immunofluorescence in control and interleukin-1beta-treated RIN-5AH cells [9].
• The cytoplasmic expression is also shown by confocal microscopy as assessed by the brightness of the cells whereas enzyme-linked immunosorbent assay detects secreted CCR3 and CCR5 molecules by comparing optical density values as these derive from the control and the treated cells [9].
• RT-PCR analysis revealed constitutive expression of CCR1, CCR2 and CCR5 mRNA [13].
• Western blot analysis demonstrated increased CCR5 protein in hippocampal tissue extracts 32 hours after lesioning [3].
• Interestingly, the expression and activation of CCR1 and CCR5 in the joint were down-regulated in the Met-RANTES group compared with the control group [14].

References