Ask about this productRelated genes to: CCR5 antibody
- Gene:
- CCR5 NIH gene
- Name:
- C-C motif chemokine receptor 5 (gene/pseudogene)
- Previous symbol:
- CMKBR5
- Synonyms:
- CKR-5, CC-CKR-5, CKR5, CD195, IDDM22
- Chromosome:
- 3p21.31
- Locus Type:
- gene with protein product
- Date approved:
- 1996-05-15
- Date modifiied:
- 2019-01-10
Related products to: CCR5 antibody
Related articles to: CCR5 antibody
- Real world inhalation exposures occur as temporally staggered mixtures of environmental pollutants and indoor allergens, yet the mechanistic consequences of sequential exposure remain poorly defined. Here, we investigated whether diesel exhaust particle (DEP) exposure primes the lung to alter subsequent responses to house dust mite (HDM) allergen independently of direct co-exposure or preexisting sensitisation. Using a murine model with defined temporal separation between exposures, we combined compartment resolved bulk transcriptomics and targeted single cell profiling to map inflammatory and cellular responses across lung tissue and airway lumen. DEP priming significantly amplified leukocyte recruitment following HDM challenge, with a dominant increase in neutrophils and no corresponding eosinophilic response. Transcriptomic analyses revealed that DEP alone preferentially induced NF-κB associated inflammatory programs, while HDM triggered both NF-κB and interferon (IFN) associated transcriptional responses. Importantly, DEP priming qualitatively reprogrammed the allergen response, enhancing both IFN stimulated gene (ISG) expression and pro-inflammatory cytokine networks. These effects were most pronounced in the airway luminal compartment, indicating a prominent inflammatory niche shaped by recruited immune cells. Single cell analyses identified expansion and activation of multiple neutrophil subpopulations, alongside recruitment of macrophage subsets, NK cells, and CD8 T cells. Ligand receptor inference and protein measurements implicated Cxcl1/Cxcl2-Cxcr2 signalling as a central axis driving neutrophil recruitment, with additional Ccr5 and Cxcr3 linked pathways contributing to broader immune cell infiltration. stimulation suggested that DEP priming enhances intrinsic cellular responsiveness to HDM, in addition to increasing the pool of responsive cells. Collectively, these findings demonstrate that pollutant exposure reprograms airway immune landscapes to amplify subsequent allergen responses, suggested through neutrophil centric and interferon linked mechanisms. This work provides a mechanistic framework for sequential exposure risk, highlights the importance of compartmentalised immune dynamics, and informs the design of advanced models for respiratory hazard assessment. - Source: PubMed
Publication date: 2026/08/17
Meldrum KirstyLeonard Martin Oliver - Artificial sweeteners, notably aspartame, are common food additives and merging environmental contaminants with potential cardiovascular risks. This study integrated network toxicology and experimental validation to explore aspartame's mechanisms in promoting cardiovascular disease (CVD). Initial toxicity prediction via ProTox 3.0 indicated cardiotoxicity among other toxicities. Potential targets of aspartame were identified using SwissTargetPrediction, ChEMBL, and SEA, while CVD associated targets were retrieved from GeneCards and OMIM and atherosclerosis related targets were obtained from GSE100927 dataset. Core targets were prioritized via STRING and Cytoscape. Functional enrichment analysis using Metascape highlighted key pathways. Molecular docking and dynamics simulations assessed binding affinity and stability. Microarray analysis, followed by in vivo and in vitro studies, validated findings. Results showed that aspartame-induced cardiovascular toxicity involves targeting IL1B, TNF, MMP9, CTSS, and CCR5, and activating cell adhesion molecules, NF-κB, and NOD-like receptor signaling pathways. In mice, aspartame reduced immune-related blood cells, impaired endothelium-dependent vasodilation, and increased vascular adhesion molecule expression. In HUVEC, the same pathways were activated. These findings suggest that aspartame promotes cardiovascular toxicity by targeting specific proteins and modulating inflammatory responses, cell migration, and adhesion via NF-κB and NOD-like receptor pathways. Collectively, this study provides mechanistic insights into aspartame-associated cardiovascular risk, providing a comprehensive mechanistic framework for a more accurate assessment. - Source: PubMed
Publication date: 2026/08/27
Chen QiuheYou HongjingWang HecaiGuan XuanchenCen XiujuanFu LantingLong LiangWang KeXu YueChen Yang - Combined antiretroviral therapy (cART) has deeply changed the approach to HIV disease treatment. cART tackles HIV replication and improves the life expectancy of HIV-infected people. Notwithstanding the effectiveness of cART in HIV infection control, several observations have determined that 15-50% of HIV-infected people display HIV-associated neurocognitive disorders (HAND) even under long-term viral suppression. Persistent production of the viral proteins Tat and gp120 by central nervous system reservoirs drives chronic neurotoxicity due to their remarkable extracellular stability and efficient uptake by neurons and glial cells. In this review, we will discuss current evidence on the molecular mechanisms by which extracellular Tat and gp120 orchestrate neurodegeneration. Four principal interconnected pathways emerge: (i) mitochondrial dysfunction; (ii) synaptodendritic injury; (iii) chronic neuroinflammation; and (iv) crosstalk with Alzheimer's disease (AD) pathways. Converging data achieved from models, Tat and gp120-transgenic mice, post-mortem tissue, and cerebrospinal fluid (CSF) biomarkers indicate that these viral proteins contribute to frontostriatal atrophy and hybrid HAND-AD phenotypes increasingly observed in aging HIV patients. Understanding these mechanisms highlights the need for adjunctive neuroprotective strategies targeting CXCR4/CCR5 signaling, mitochondrial quality control, inflammatory pathways, and Aβ/Tau homeostasis derangement and supports the integration of multimodal neuroimaging and CSF proteomics in future longitudinal studies aimed at improving diagnosis and therapeutic development. - Source: PubMed
Publication date: 2026/08/12
Cecchetto RiccardoDiani EricaLotti VirginiaPalmisano AsiaLagni AnnaMantoan MarcoTurrina StefaniaRaniero DarioPaolone GiovannaMazzariol AnnaritaGibellini Davide - Maraviroc (MVC), a CCR5 antagonist, has been proposed as a potential antiviral agent against SARS-CoV-2; however, its mechanism of action across viral variants remains unclear. Here, we evaluated the antiviral activity of MVC against SARS-CoV-2 wild-type (WT) and Omicron BA.1 variants using single-round infectious particles (SRIPs), virus-like particles (VLPs), and cell-based assays, with a focus on its impact on viral entry and Mpro function. MVC potently inhibited infection of both WT and BA.1 SRIPs in Vero E6 cells, exhibiting EC values of 0.0065 μM and 0.016 μM, respectively. Time-of-addition assays revealed that MVC primarily targets the early phase of infection, with the strongest inhibition observed at the viral entry stage, while moderate effects were detected during attachment and post-entry stages. Fluorescence-labeled VLP imaging demonstrated distinct entry pathways, with WT predominantly entering via plasma membrane fusion and BA.1 via endocytosis, independent of cell type. MVC altered WT-VLP trafficking by promoting internalization and lysosomal localization, whereas it had minimal impact on BA.1 internalization. In spike-mediated cell-cell fusion assays, MVC preferentially inhibited WT spike-driven syncytium formation but showed limited effects on BA.1 or BA.4 fusion, while more effectively reducing Omicron spike-mediated binding. At the post-entry stage, MVC inhibited SARS-CoV-2 main protease (Mpro) activity, with BA.1 Mpro (P132H) exhibiting greater sensitivity (IC = 0.496 µM) than WT (1.869 µM). Collectively, these findings demonstrate that MVC exerts variant-dependent antiviral effects by targeting viral entry, modulating trafficking pathways, and inhibiting Mpro activity. This study highlights MVC as a multi-stage inhibitor with differential efficacy against SARS-CoV-2 variants, providing insights into its potential therapeutic application. - Source: PubMed
Publication date: 2026/08/19
Le Uyen Nguyen PhuongChen Po-JuChu Li-WeiArifin Jane CynthiaChen Chih-HaoChen Yu-HsuanSu Wen-ChiHsueh Po-RenPing Yueh-HsinLin Cheng-Wen - Most patients with solid tumors do not respond to immune checkpoint blockade, and inadequate T cell infiltration of the tumor parenchyma is the dominant mechanism of primary resistance. Oncolytic viruses address this problem by a distinct route: they replicate selectively within tumor cells, produce immunogenic cell death, and convert infected cells into local sources of any encoded transgene. Most armed designs to date have carried cytokine or checkpoint-antibody payloads, and chemokines have attracted comparatively little attention despite bearing directly on the trafficking bottleneck. This review synthesizes the preclinical literature on chemokine-armed oncolytic viruses across three receptor axes: CXCR3 (CXCL9, CXCL10, CXCL11), CCR5 (CCL5/RANTES), and CCR7 (CCL19). The accumulated evidence indicates that therapeutic outcome depends less on the chemokine payload itself than on the interaction between payload and viral backbone. CXCL11 outperforms its sister CXCR3 ligands not through intrinsic potency but because it is non-redundant with the endogenous chemokines induced by vesicular stomatitis virus and vaccinia, and because it largely escapes proteolytic cleavage by dipeptidyl peptidase 4 (DPP4). CCL5 has shown the most consistent activity in dual-payload designs that pair chemotaxis with a T cell survival cytokine such as IL-15. CCL19, which addresses lymphoid organization rather than effector recruitment, rests on a single published construct. One evidence gap is central: no head-to-head comparison of chemokine payloads within a single viral platform has been published. We therefore propose a translational decision framework that aligns chemokine selection with the immune contexture of the target tumor. - Source: PubMed
Publication date: 2026/07/31
Alwithenani Akram