-
International Immunopharmacology Dec 2021MCP-1 (Monocyte chemoattractant protein-1), also known as Chemokine (CC-motif) ligand 2 (CCL2), is from family of CC chemokines. It has a vital role in the process of... (Review)
Review
MCP-1 (Monocyte chemoattractant protein-1), also known as Chemokine (CC-motif) ligand 2 (CCL2), is from family of CC chemokines. It has a vital role in the process of inflammation, where it attracts or enhances the expression of other inflammatory factors/cells. It leads to the advancement of many disorders by this main mechanism of migration and infiltration of inflammatory cells like monocytes/macrophages and other cytokines at the site of inflammation. MCP-1 has been inculpated in the pathogenesis of numerous disease conditions either directly or indirectly like novel corona virus, cancers, neuroinflammatory diseases, rheumatoid arthritis, cardiovascular diseases. The elevated MCP-1 level has been observed in COVID-19 patients and proven to be a biomarker associated with the extremity of disease along with IP-10. This review will focus on involvement and role of MCP-1 in various pathological conditions.
Topics: Animals; Biomarkers; Chemokine CCL2; Chemotaxis; Disease; Humans; Monocytes; Oxidative Stress
PubMed: 34233864
DOI: 10.1016/j.intimp.2021.107598 -
International Journal of Molecular... Oct 2020CC chemokines (or β-chemokines) are 28 chemotactic cytokines with an N-terminal CC domain that play an important role in immune system cells, such as CD4 and CD8... (Review)
Review
CC chemokines (or β-chemokines) are 28 chemotactic cytokines with an N-terminal CC domain that play an important role in immune system cells, such as CD4 and CD8 lymphocytes, dendritic cells, eosinophils, macrophages, monocytes, and NK cells, as well in neoplasia. In this review, we discuss human CC motif chemokine ligands: CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 (CC motif chemokine receptor CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 ligands). We present their functioning in human physiology and in neoplasia, including their role in the proliferation, apoptosis resistance, drug resistance, migration, and invasion of cancer cells. We discuss the significance of chemokine receptors in organ-specific metastasis, as well as the influence of each chemokine on the recruitment of various cells to the tumor niche, such as cancer-associated fibroblasts (CAF), Kupffer cells, myeloid-derived suppressor cells (MDSC), osteoclasts, tumor-associated macrophages (TAM), tumor-infiltrating lymphocytes (TIL), and regulatory T cells (T). Finally, we show how the effect of the chemokines on vascular endothelial cells and lymphatic endothelial cells leads to angiogenesis and lymphangiogenesis.
Topics: Animals; Cell Proliferation; Chemokines, CC; Humans; Neoplasms; Receptors, CCR; Signal Transduction; Tumor Microenvironment
PubMed: 33076281
DOI: 10.3390/ijms21207619 -
International Journal of Molecular... Jul 2020Chemokines, which are basic proteins that exert their effects via G protein-coupled receptors and a subset of the cytokine family, are mediators deeply involved in... (Review)
Review
Chemokines, which are basic proteins that exert their effects via G protein-coupled receptors and a subset of the cytokine family, are mediators deeply involved in leukocyte migration during an inflammatory reaction. Chemokine (C-C motif) ligand 20 (CCL20), also known as macrophage inflammatory protein (MIP)-3α, liver activation regulated chemokine (LARC), and Exodus-1, is a small protein that is physiologically expressed in the liver, colon, and skin, is involved in tissue inflammation and homeostasis, and has a specific receptor chemokine receptor 6 (CCR6). The CCL20-CCR6 axis has long been known to be involved in inflammatory and infectious diseases, such as rheumatoid arthritis and human immunodeficiency virus infections. Recently, however, reports have shown that the CCL20-CCR6 axis is associated with several cancers, including hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, cervical cancer, and kidney cancer. The CCL20-CCR6 axis promotes cancer progression directly by enhancing migration and proliferation of cancer cells and indirectly by remodeling the tumor microenvironment through immune cell control. The present article reviewed the role of the CCL20-CCR6 axis in cancer progression and its potential as a therapeutic target.
Topics: Cell Movement; Cell Proliferation; Chemokine CCL20; Chemokines; Disease Progression; Humans; Macrophages; Neoplasms; Receptors, CCR6; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Tumor Microenvironment
PubMed: 32707869
DOI: 10.3390/ijms21155186 -
Biomedicine & Pharmacotherapy =... Jan 2022Gastric cancer (GC) is the world's second-leading cause of cancer-related mortality, continuing to make it a serious healthcare concern. Even though the prevalence of GC...
BACKGROUND
Gastric cancer (GC) is the world's second-leading cause of cancer-related mortality, continuing to make it a serious healthcare concern. Even though the prevalence of GC reduces, the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers to diagnose early GC and predict chemosensitivity and recurrence.
METHODS AND MATERIAL
We integrated the gene expression patterns of gastric cancers from four RNAseq datasets (GSE113255, GSE142000, GSE118897, and GSE130823) from Gene Expression Omnibus (GEO) database to recognize differentially expressed genes (DEGs) between normal and GC samples. A gene co-expression network was built using weighted co-expression network analysis (WGCNA). Furthermore, RT-qPCR was performed to validate the in silico results.
RESULTS
The red modules in GSE113255, Turquoise in GSE142000, Brown in GSE118897, and the green-yellow module in GSE130823 datasets were found to be highly correlated with the anatomical site of GC. ITGAX, CCL14, ADHFE1, and HOXB13) as the hub gene are differentially expressed in tumor and non-tumor gastric tissues in this study. RT-qPCR demonstrated a high level of the expression of this gene.
CONCLUSION
The expression levels of ITGAX, CCL14, ADHFE1, and HOXB13 in GC tumor tissues are considerably greater than in adjacent normal tissues. Systems biology approaches identified that these genes could be possible GC marker genes, providing ideas for other experimental studies in the future.
Topics: Alcohol Oxidoreductases; Biomarkers, Tumor; Chemokines, CC; Computational Biology; Early Detection of Cancer; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Homeodomain Proteins; Humans; Mitochondrial Proteins; Prognosis; Stomach Neoplasms
PubMed: 34864309
DOI: 10.1016/j.biopha.2021.112477 -
Frontiers in Immunology 2022The CCL2-CCR2 axis is one of the major chemokine signaling pathways that has received special attention because of its function in the development and progression of... (Review)
Review
The CCL2-CCR2 axis is one of the major chemokine signaling pathways that has received special attention because of its function in the development and progression of cardiovascular disease. Numerous investigations have been performed over the past decades to explore the function of the CCL2-CCR2 signaling axis in cardiovascular disease. Laboratory data on the CCL2-CCR2 axis for cardiovascular disease have shown satisfactory outcomes, yet its clinical translation remains challenging. In this article, we describe the mechanisms of action of the CCL2-CCR2 axis in the development and evolution of cardiovascular diseases including heart failure, atherosclerosis and coronary atherosclerotic heart disease, hypertension and myocardial disease. Laboratory and clinical data on the use of the CCL2-CCR2 pathway as a targeted therapy for cardiovascular diseases are summarized. The potential of the CCL2-CCR2 axis in the treatment of cardiovascular diseases is explored.
Topics: Cardiovascular Diseases; Chemokine CCL2; Humans; Receptors, CCR2; Signal Transduction
PubMed: 36110847
DOI: 10.3389/fimmu.2022.975367 -
Nature Communications Aug 2021The presence or absence of anti-citrullinated peptide antibodies (ACPA) and associated disparities in patients with rheumatoid arthritis (RA) implies disease...
The presence or absence of anti-citrullinated peptide antibodies (ACPA) and associated disparities in patients with rheumatoid arthritis (RA) implies disease heterogeneity with unknown diverse immunopathological mechanisms. Here we profile CD45 hematopoietic cells from peripheral blood or synovial tissues from both ACPA+ and ACPA- RA patients by single-cell RNA sequencing and identify subsets of immune cells that contribute to the pathogenesis of RA subtypes. We find several synovial immune cell abnormalities, including up-regulation of CCL13, CCL18 and MMP3 in myeloid cell subsets of ACPA- RA compared with ACPA+ RA. Also evident is a lack of HLA-DRB5 expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of patients with ACPA- RA. Furthermore, the HLA-DR15 haplotype (DRB1/DRB5) conveys an increased risk of developing active disease in ACPA+ RA in a large cohort of patients with treatment-naive RA. Immunohistochemical staining shows increased infiltration of CCL13 and CCL18-expressing immune cells in synovial tissues of ACPA- RA. Collectively, our data provide evidence of the differential involvement of cellular and molecular pathways involved in the pathogenesis of seropositive and seronegative RA subtypes and reveal the importance of precision therapy based on ACPA status.
Topics: Anti-Citrullinated Protein Antibodies; Arthritis, Rheumatoid; Autoantibodies; Cell Line; Chemokines, CC; Cohort Studies; Genetic Predisposition to Disease; HLA-DR Serological Subtypes; Humans; Killer Cells, Natural; Leukocyte Common Antigens; Matrix Metalloproteinase 3; Monocyte Chemoattractant Proteins; Myeloid Cells; Synovial Membrane; T-Lymphocytes; Up-Regulation
PubMed: 34404786
DOI: 10.1038/s41467-021-25246-7 -
Proceedings of the National Academy of... Jun 2020Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We...
Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease ( < 4 × 10, < 4 × 10), and plasma CCL20 was associated with disease severity ( = 4 × 10), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.
Topics: Adult; Biomarkers; Case-Control Studies; Chemokine CCL11; Chemokine CCL20; Cohort Studies; Female; Humans; Inflammation; Male; Middle Aged; Multiple Sclerosis; Prognosis; Proteomics; Reproducibility of Results; Severity of Illness Index; Young Adult
PubMed: 32457139
DOI: 10.1073/pnas.1912839117 -
JCI Insight Feb 2023Patients with nonalcoholic steatohepatitis (NASH) have increased expression of liver monocyte chemoattractant protein-1 (MCP-1), but its cellular source and contribution...
Patients with nonalcoholic steatohepatitis (NASH) have increased expression of liver monocyte chemoattractant protein-1 (MCP-1), but its cellular source and contribution to various aspects of NASH pathophysiology remain debated. We demonstrated increased liver CCL2 (which encodes MCP-1) expression in patients with NASH, and commensurately, a 100-fold increase in hepatocyte Ccl2 expression in a mouse model of NASH, accompanied by increased liver monocyte-derived macrophage (MoMF) infiltrate and liver fibrosis. To test repercussions of increased hepatocyte-derived MCP-1, we generated hepatocyte-specific Ccl2-knockout mice, which showed reduced liver MoMF infiltrate as well as decreased liver fibrosis. Forced hepatocyte MCP-1 expression provoked the opposite phenotype in chow-fed wild-type mice. Consistent with increased hepatocyte Notch signaling in NASH, we observed a close correlation between markers of Notch activation and CCL2 expression in patients with NASH. We found that an evolutionarily conserved Notch/recombination signal binding protein for immunoglobulin kappa J region binding site in the Ccl2 promoter mediated transactivation of the Ccl2 promoter in NASH diet-fed mice. Increased liver MoMF infiltrate and liver fibrosis seen in opposite gain-of-function mice was ameliorated with concomitant hepatocyte Ccl2 knockout or CCR2 inhibitor treatment. Hepatocyte Notch activation prompts MCP-1-dependent increase in liver MoMF infiltration and fibrosis.
Topics: Animals; Mice; Chemokine CCL2; Hepatocytes; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
PubMed: 36752206
DOI: 10.1172/jci.insight.165369 -
The Journal of Experimental Medicine Aug 2022Circulating proteomic signatures of age are closely associated with aging and age-related diseases; however, the utility of changes in secreted proteins in identifying...
Circulating proteomic signatures of age are closely associated with aging and age-related diseases; however, the utility of changes in secreted proteins in identifying therapeutic targets for diseases remains unclear. Serum proteomic profiling of an age-stratified healthy population and further community-based cohort together with heart failure patients study demonstrated that circulating C-C motif chemokine ligand 17 (CCL17) level increased with age and correlated with cardiac dysfunction. Subsequent animal experiments further revealed that Ccll7-KO significantly repressed aging and angiotensin II (Ang II)-induced cardiac hypertrophy and fibrosis, accompanied by the plasticity and differentiation of T cell subsets. Furthermore, the therapeutic administration of an anti-CCL17 neutralizing antibody inhibited Ang II-induced pathological cardiac remodeling. Our findings reveal that chemokine CCL17 is identifiable as a novel therapeutic target in age-related and Ang II-induced pathological cardiac hypertrophy and heart failure.
Topics: Angiotensin II; Animals; Cardiomegaly; Chemokine CCL17; Chemokines; Fibrosis; Heart Failure; Humans; Ligands; Mice; Mice, Inbred C57BL; Myocardium; Myocytes, Cardiac; Proteomics
PubMed: 35687056
DOI: 10.1084/jem.20200418 -
Nature Communications Apr 2022Metastatic non-small cell lung cancer (NSCLC) remains largely incurable and the prognosis is extremely poor once it spreads to the brain. In particular, in patients with...
Metastatic non-small cell lung cancer (NSCLC) remains largely incurable and the prognosis is extremely poor once it spreads to the brain. In particular, in patients with brain metastases, the blood brain barrier (BBB) remains a significant obstacle for the biodistribution of antitumor drugs and immune cells. Here we report that chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR) exhibit antitumor activity in vitro against tumor cell lines and lung cancer organoids, and in vivo in xenotransplant models of orthotopic and metastatic NSCLC. The co-expression of the CCL2 receptor CCR2b in B7-H3.CAR-T cells, significantly improves their capability of passing the BBB, providing enhanced antitumor activity against brain tumor lesions. These findings indicate that leveraging T-cell chemotaxis through CCR2b co-expression represents a strategy to improve the efficacy of adoptive T-cell therapies in patients with solid tumors presenting with brain metastases.
Topics: Brain; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Chemokine CCL2; Humans; Lung Neoplasms; Receptors, Chimeric Antigen; T-Lymphocytes; Tissue Distribution; Xenograft Model Antitumor Assays
PubMed: 35443752
DOI: 10.1038/s41467-022-29647-0