Редактирование: CCR3 (раздел)

==Publications==

{{medline-entry
|title=Low Molecular Weight Hyaluronan Induces an Inflammatory Response in Ovarian Stromal Cells and Impairs Gamete Development In Vitro.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32033185
|abstract=The ovarian stroma, the microenvironment in which female gametes grow and mature, becomes inflamed and fibrotic with age. Hyaluronan is a major component of the ovarian extracellular matrix (ECM), and in other aging tissues, accumulation of low molecular weight (LMW) hyaluronan fragments can drive inflammation. Thus, we hypothesized that LMW hyaluronan fragments contribute to female reproductive aging by stimulating an inflammatory response in the ovarian stroma and impairing gamete quality. To test this hypothesis, isolated mouse ovarian stromal cells or secondary stage ovarian follicles were treated with physiologically relevant (10 or 100 μg/mL) concentrations of 200 kDa LMW hyaluronan. In ovarian stromal cells, acute LMW hyaluronan exposure, at both doses, resulted in the secretion of a predominantly type 2 (Th2) inflammatory cytokine profile as revealed by a cytokine antibody array of conditioned media. Additional qPCR analyses of ovarian stromal cells demonstrated a notable up-regulation of the eotaxin receptor Ccr3 and activation of genes involved in eosinophil recruitment through the [[IL5]]-[[CCR3]] signaling pathway. These findings were consistent with an age-dependent increase in ovarian stromal expression of Ccl11, a major [[CCR3]] ligand. When ovarian follicles were cultured in 10 or 100 μg/mL LMW hyaluronan for 12 days, gametes with compromised morphology and impaired meiotic competence were produced. In the 100 μg/mL condition, LMW hyaluronan induced premature meiotic resumption, ultimately leading to in vitro aging of the resulting eggs. Further, follicles cultured in this LMW hyaluronan concentration produced significantly less estradiol, suggesting compromised granulosa cell function. Taken together, these data demonstrate that bioactive LMW hyaluronan fragments may contribute to reproductive aging by driving an inflammatory stromal milieu, potentially through eosinophils, and by directly compromising gamete quality through impaired granulosa cell function.
|mesh-terms=* Aging
* Animals
* Extracellular Matrix
* Female
* Germ Cells
* Granulosa Cells
* Hyaluronan Receptors
* Hyaluronic Acid
* Inflammation
* Mice
* Mice, Inbred BALB C
* Mice, Inbred C57BL
* Molecular Weight
* Ovary
* Stromal Cells
|keywords=* hyaluronan fragments
* inflammation
* ovarian biology
* reproductive aging
* stroma
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036885
}}
{{medline-entry
|title=Early life allergen and air pollutant exposures alter longitudinal blood immune profiles in infant rhesus monkeys.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28529118
|abstract=Early life is a critical period for the progressive establishment of immunity in response to environmental stimuli; the impact of airborne challenges on this process is not well defined. In a longitudinal fashion, we determined the effect of episodic house dust mite (HDM) aerosol and ozone inhalation, both separately and combined, on peripheral blood immune cell phenotypes and cytokine expression from 4 to 25weeks of age in an infant rhesus monkey model of childhood development. Immune profiles in peripheral blood were compared with lung lavage at 25weeks of age. Independent of exposure, peripheral blood cell counts fluctuated with chronologic age of animals, while IFNγ and IL-4 mRNA levels increased over time in a linear fashion. At 12weeks of age, total WBC, lymphocyte numbers, FoxP3 mRNA and IL-12 mRNA were dramatically reduced relative to earlier time points, but increased to a steady state with age. Exposure effects were observed for monocyte numbers, as well as [[CCR3]], FoxP3, and IL-12 mRNA levels in peripheral blood. Significant differences in cell surface marker and cytokine expression were detected following in vitro HDM or PMA/ionomycin stimulation of PBMC isolated from animals exposed to either HDM or ozone. Lavage revealed a mixed immune phenotype of FoxP3, IFNγ and eosinophilia in association with combined HDM plus ozone exposure, which was not observed in blood. Collectively, our findings show that airborne challenges during postnatal development elicit measureable cell and cytokine changes in peripheral blood over time, but exposure-induced immune profiles are not mirrored in the lung.
|mesh-terms=* Aerosols
* Aging
* Air Pollutants
* Allergens
* Animals
* Antigens, Dermatophagoides
* Blood
* Bronchoalveolar Lavage Fluid
* Gene Expression Regulation
* Inhalation Exposure
* Interferon-gamma
* Macaca mulatta
* Male
* Monocytes
|keywords=* Cytokine
* House dust mite
* Infant
* Ozone
* Peripheral blood
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535809
}}
{{medline-entry
|title=An emerging role for eotaxins in neurodegenerative disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27664933
|abstract=Eotaxins are C-C motif chemokines first identified as potent eosinophil chemoattractants. They facilitate eosinophil recruitment to sites of inflammation in response to parasitic infections as well as allergic and autoimmune diseases such as asthma, atopic dermatitis, and inflammatory bowel disease. The eotaxin family currently includes three members: eotaxin-1 ([[CCL11]]), eotaxin-2 (CCL24), and eotaxin-3 (CCL26). Despite having only ~30% sequence homology to one another, each was identified based on its ability to bind the chemokine receptor, [[CCR3]]. Beyond their role in innate immunity, recent studies have shown that [[CCL11]] and related molecules may directly contribute to degenerative processes in the central nervous system (CNS). [[CCL11]] levels increase in the plasma and cerebrospinal fluid of both mice and humans as part of normal aging. In mice, these increases are associated with declining neurogenesis and impaired cognition and memory. In humans, elevated plasma levels of [[CCL11]] have been observed in Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and secondary progressive multiple sclerosis when compared to age-matched, healthy controls. Since [[CCL11]] is capable of crossing the blood-brain barrier of normal mice, it is plausible that eotaxins generated in the periphery may exert physiological and pathological actions in the CNS. Here, we briefly review known functions of eotaxin family members during innate immunity, and then focus on whether and how these molecules might participate in the progression of neurodegenerative diseases.
|mesh-terms=* Aging
* Animals
* Chemokine CCL11
* Chemokine CCL24
* Chemokine CCL26
* Humans
* Immunity, Innate
* Neurodegenerative Diseases
* Receptors, CCR3
|keywords=* Aging
* CCL11
* Eotaxin
* Multiple sclerosis
* Neurodegeneration
* Neurogenesis
|full-text-url=https://sci-hub.do/10.1016/j.clim.2016.09.010
}}
{{medline-entry
|title=Overcoming the aging systemic milieu to restore neural stem cell function.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22175510
|abstract=As mammals age, the rate of neurogenesis in the brain declines with a concomitant reduction in cognitive ability. Recent data suggest that plasma-borne factors are responsible for inhibition of neurogenesis. When the circulatory systems of old and young mice are connected, the old mice experience increased neurogenesis and the young mice exhibit less neurogenesis, suggesting the importance of systemic circulating factors. Chemokine [[CCL11]]/eotaxin has been identified as a factor that increases with aging. Injections of [[CCL11]] inhibit neurogenesis in young mice, an effect likely mediated by [[CCR3]] receptors on neural stem cells. Identification of a specific factor that plays a causative role in stem cell dysfunction in aging is consistent with data showing that transforming growth factor-β (TGF-β) inhibits satellite cell-mediated repair. Together, these data suggest that the systemic milieu plays a critical role in the aging of adult stem cells. Because adult stem cells help maintain homeostasis by providing the possibility of replacing metabolically damaged differentiated cells, aging of the systemic milieu and stem cell niches may drive functional decline during aging. The identification of a specific systemic change suggests that aging is more amenable to therapeutic modulation than work on global metabolism-derived damage and cellular senescence implies.
|mesh-terms=* Aging
* Animals
* Brain
* Cellular Senescence
* Chemokine CCL11
* Cognition
* Immune System
* Memory
* Mice
* Neural Stem Cells
* Neurogenesis
* Receptors, CCR3
* Stem Cells
* Transforming Growth Factor beta

|full-text-url=https://sci-hub.do/10.1089/rej.2011.1301
}}
{{medline-entry
|title=Upregulation of [[CCR3]] by age-related stresses promotes choroidal endothelial cell migration via VEGF-dependent and -independent signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21917937
|abstract=To explore the molecular mechanisms by which the C-C chemokine receptor type 3 ([[CCR3]]) and chemokine (C-C motif) ligand 11 ([[CCL11]]) regulate choroidal endothelial cell (CEC) migration and the interactions with the vascular endothelial growth factor (VEGF) signaling pathway. Human retinal sections from young and aged donor normal eyes were immunolabeled. By real-time PCR, [[CCR3]] mRNA was measured in retinal pigmented epithelium (RPE)/choroids obtained from young and aged human donor eyes and in cultured CECs exposed to hydrogen peroxide. [[CCR3]] ligand and [[CCL11]]- or VEGF-stimulated CEC migration was also measured in the presence of the [[CCR3]] inhibitor or control using fluorescence microscopy. Activation of Rac1, phosphorylated Akt as a readout for phosphoinositol 3-kinase signaling, and VEGFR2 activation were measured in CECs incubated with [[CCL11]], VEGF, or combined [[CCL11]]/VEGF. [[CCR3]] was expressed to a greater level in older compared with that in younger human retinas or RPE/choroids. Ligand-activated [[CCR3]] increased CEC migration, which was inhibited by the [[CCR3]] inhibitor. Rac1 activity, p-Akt, and p-VEGFR2 were significantly increased in CECs incubated with [[CCL11]]. The [[CCR3]] inhibitor prevented VEGF-induced CEC migration and Rac1 activation in CECs. Rac1 activity was additively increased in CECs treated with [[CCL11]] and VEGF compared with that in cells with [[CCL11]] or VEGF treatment alone. Ligand-activated [[CCR3]] caused VEGFR2 phosphorylation and coimmunoprecipitation of VEGFR2 and [[CCR3]]. Activated [[CCR3]] promotes CEC migration and Rac1 activation and causes an association with and activation of VEGFR2. Cross-talk between [[CCR3]] and VEGF signaling exists and may be important in choroidal neovascularization in human age-related macular degeneration.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Cell Movement
* Cells, Cultured
* Chemokine CCL11
* Choroid
* Choroid Neoplasms
* Endothelial Cells
* Humans
* Macular Degeneration
* Receptor Cross-Talk
* Receptors, CCR3
* Retinal Pigment Epithelium
* Signal Transduction
* Stress, Physiological
* Up-Regulation
* Vascular Endothelial Growth Factor A
* Vascular Endothelial Growth Factor Receptor-2
* Young Adult
* rac1 GTP-Binding Protein

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208059
}}
{{medline-entry
|title=The chemokine (C-C-motif) receptor 3 ([[CCR3]]) gene is linked and associated with age at menarche in Caucasian females.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17146638
|abstract=Chemokine (C-C-motif) receptor 3 ([[CCR3]]), playing an important role in endometrium related metabolic pathways, may influence the onset of menarche. To test linkage and/or association between [[CCR3]] polymorphisms with the variation of age at menarche (AAM) in Caucasian females, we recruited a sample of 1,048 females from 354 Caucasian nuclear families and genotyped 16 SNPs spanning the entire [[CCR3]] gene. Linkage disequilibrium and haplotype blocks were inferred by Haploview. Both single-SNP markers and haplotypes were tested for linkage and/or association with AAM using QTDT (quantitative transmission disequilibrium test). We also tested associations between [[CCR3]] polymorphisms and AAM in a selected random sample of daughters using ANOVA (analysis of variance). We identified two haplotype blocks. Only block two showed significant results. After correction for multiple testing, significant total associations of SNP7, SNP9 with AAM were detected (P = 0.009 and 0.006, respectively). We also detected significant within-family association of SNP9 (P = 0.01). SNP14 was linked to AAM (P = 0.02) at the nominal level. In addition, there was evidence of significant total association and nominal significant linkage (P = 0.008 and 0.03, respectively) with AAM for the haplotype [[AGA]] reconstructed by SNP7, SNP9 and SNP13. ANOVA confirmed the results by QTDT. For the first time we reported that [[CCR3]] is linked and associated with AAM variation in Caucasian women. However, further studies are necessary to substantiate our conclusions.
|mesh-terms=* Aging
* Alleles
* Amino Acid Motifs
* Endometrium
* European Continental Ancestry Group
* Female
* Genetic Linkage
* Humans
* Male
* Menarche
* Polymorphism, Single Nucleotide
* Random Allocation
* Receptors, CCR3
* Receptors, Chemokine

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1829487
}}
{{medline-entry
|title=RANTES and [[MIP]]-1alpha production by T lymphocytes, monocytes and NK cells from nonagenarian subjects.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11772507
|abstract=While numerous previous studies have investigated age-related changes of cytokine production, little is known about chemokines, the importance of which in regulating immune response is becoming increasingly evident. In this study, a group of healthy subjects over 90 years old is compared to a group of young subjects, we evaluated the ability of monocytes, T lymphocytes and NK cells: (1) to produce RANTES and [[MIP]]-1alpha, either in basal conditions or after stimulation with, respectively, LPS, anti-CD3 MoAb and IL-2; (2) to express the corresponding chemokine receptors ([[CCR1]], [[CCR3]], [[CCR5]]). We demonstrate that: (a) monocytes, T lymphocytes and NK cells spontaneously produced detectable amounts of chemokines, both in young and old subjects; (b) monocyte-dependent RANTES and [[MIP]]-1alpha production induced by LPS was up-regulated in nonagenarian subjects as anti-CD3-induced secretion from T cells; (c) RANTES and [[MIP]]-1alpha production by IL-2 stimulated NK cells was reduced in elderly subjects; (d) [[CCR1]], [[CCR3]] and [[CCR5]] were widely expressed on monocytes, but less expressed on T lymphocytes and NK cells. The diversity within PBMC might reflect their different states of activation and/or responsiveness, influencing the ability to develop rapid innate and long-lasting adaptive immune responses.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Cells, Cultured
* Chemokine CCL3
* Chemokine CCL4
* Chemokine CCL5
* Female
* Humans
* Killer Cells, Natural
* Lipopolysaccharides
* Macrophage Inflammatory Proteins
* Male
* Monocytes
* Receptors, CCR1
* Receptors, CCR3
* Receptors, CCR5
* Receptors, Chemokine
* T-Lymphocytes

|full-text-url=https://sci-hub.do/10.1016/s0531-5565(01)00187-5
}}
{{medline-entry
|title=Expression pattern of [[CXCR3]], [[CXCR4]], and [[CCR3]] chemokine receptors in the developing human brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11202173
|abstract=Chemokine receptors are essential components of the immune and central nervous systems, but little is known about their distribution during development. We evaluated the distribution of 3 chemokine receptors: [[CXCR3]], [[CXCR4]], and [[CCR3]] in the human developing brain. Of these, [[CXCR3]] was the only receptor expressed in fetal brain at 26 wk of gestation and its expression was restricted to glial cells, endothelial cells, and the choroid plexus. Neuronal staining was only seen at term in the Purkinje cells of the cerebellum. [[CCR3]] appeared only at term in both neurons and glial cells. The expression pattern of these 2 receptors in the late gestation and term resembled that of adults. [[CXCR4]] could not be detected in the fetal brain on neurons nor on glial cells. By examining pediatric cases, we determined that [[CXCR4]] expression commences sometimes between 3.5 and 4.5 yr. Two of the chemokine receptors examined, [[CCR3]] and [[CXCR4]], can be used as co-receptor together with [[CD4]] for HIV entry, but neither was expressed during the second trimester of pregnancy. Our findings suggest that it is unlikely that [[CCR3]] or [[CXCR4]] play a major role in HIV-1 transmission in the fetal brain before 37 wk of gestation.
|mesh-terms=* Adolescent
* Aging
* Brain
* Child
* Child, Preschool
* Embryonic and Fetal Development
* Fetus
* Humans
* Immunohistochemistry
* Infant
* Infant, Newborn
* Receptors, CCR3
* Receptors, CXCR3
* Receptors, CXCR4
* Receptors, Chemokine

|full-text-url=https://sci-hub.do/10.1093/jnen/60.1.25
}}