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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 -
Frontiers in Immunology 2019Immunotherapy is a clinically validated treatment for many cancers to boost the immune system against tumor growth and dissemination. Several strategies are used to... (Review)
Review
Immunotherapy is a clinically validated treatment for many cancers to boost the immune system against tumor growth and dissemination. Several strategies are used to harness immune cells: monoclonal antibodies against tumor antigens, immune checkpoint inhibitors, vaccination, adoptive cell therapies (e.g., CAR-T cells) and cytokine administration. In the last decades, it is emerging that the chemokine system represents a potential target for immunotherapy. Chemokines, a large family of cytokines with chemotactic activity, and their cognate receptors are expressed by both cancer and stromal cells. Their altered expression in malignancies dictates leukocyte recruitment and activation, angiogenesis, cancer cell proliferation, and metastasis in all the stages of the disease. Here, we review first attempts to inhibit the chemokine system in cancer as a monotherapy or in combination with canonical or immuno-mediated therapies. We also provide recent findings about the role in cancer of atypical chemokine receptors that could become future targets for immunotherapy.
Topics: Antibodies, Monoclonal, Humanized; Benzylamines; Chemokines, CC; Chemokines, CXC; Cyclams; Heterocyclic Compounds; Humans; Immunotherapy; Molecular Targeted Therapy; Neoplasms; Receptors, CCR; Receptors, CXCR
PubMed: 30894861
DOI: 10.3389/fimmu.2019.00379 -
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 -
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 -
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 -
Einstein (Sao Paulo, Brazil) 2015Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15kDa. Chemokines and their receptors are able to control the... (Review)
Review
Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15kDa. Chemokines and their receptors are able to control the migration and residence of all immune cells. Some chemokines are considered pro-inflammatory, and their release can be induced during an immune response at a site of infection, while others are considered homeostatic and are involved in controlling of cells migration during tissue development or maintenance. The physiologic importance of this family of mediators is resulting from their specificity - members of the chemokine family induce recruitment of well-defined leukocyte subsets. There are two major chemokine sub-families based upon cysteine residues position: CXC and CC. As a general rule, members of the CXC chemokines are chemotactic for neutrophils, and CC chemokines are chemotactic for monocytes and sub-set of lymphocytes, although there are some exceptions. This review discusses the potential role of chemokines in inflammation focusing on the two best-characterized chemokines: monocyte chemoattractant protein-1, a CC chemokine, and interleukin-8, a member of the CXC chemokine sub-family.
Topics: Acute Disease; Chemokine CCL2; Chemokines; Humans; Inflammation; Interleukin-8; Peptide Fragments
PubMed: 26466066
DOI: 10.1590/S1679-45082015RB3438 -
Cell Nov 2017The two oncogenes KRas and Myc cooperate to drive tumorigenesis, but the mechanism underlying this remains unclear. In a mouse lung model of KRas-driven adenomas, we...
The two oncogenes KRas and Myc cooperate to drive tumorigenesis, but the mechanism underlying this remains unclear. In a mouse lung model of KRas-driven adenomas, we find that co-activation of Myc drives the immediate transition to highly proliferative and invasive adenocarcinomas marked by highly inflammatory, angiogenic, and immune-suppressed stroma. We identify epithelial-derived signaling molecules CCL9 and IL-23 as the principal instructing signals for stromal reprogramming. CCL9 mediates recruitment of macrophages, angiogenesis, and PD-L1-dependent expulsion of T and B cells. IL-23 orchestrates exclusion of adaptive T and B cells and innate immune NK cells. Co-blockade of both CCL9 and IL-23 abrogates Myc-induced tumor progression. Subsequent deactivation of Myc in established adenocarcinomas triggers immediate reversal of all stromal changes and tumor regression, which are independent of CD4CD8 T cells but substantially dependent on returning NK cells. We show that Myc extensively programs an immune suppressive stroma that is obligatory for tumor progression.
Topics: Adenocarcinoma; Adenoma; Animals; Carcinogenesis; Chemokines, CC; Disease Models, Animal; Female; Inflammation; Interleukin-23; Lung Neoplasms; Macrophage Inflammatory Proteins; Macrophages; Male; Mice; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins p21(ras); Tumor Microenvironment
PubMed: 29195074
DOI: 10.1016/j.cell.2017.11.013 -
Cancer Discovery Mar 2020Regulatory T cells (Treg) are abundant in human and mouse pancreatic cancer. To understand the contribution to the immunosuppressive microenvironment, we depleted Tregs...
Regulatory T cells (Treg) are abundant in human and mouse pancreatic cancer. To understand the contribution to the immunosuppressive microenvironment, we depleted Tregs in a mouse model of pancreatic cancer. Contrary to our expectations, Treg depletion failed to relieve immunosuppression and led to accelerated tumor progression. We show that Tregs are a key source of TGFβ ligands and, accordingly, their depletion reprogramed the fibroblast population, with loss of tumor-restraining, smooth muscle actin-expressing fibroblasts. Conversely, we observed an increase in chemokines , and leading to increased myeloid cell recruitment, restoration of immune suppression, and promotion of carcinogenesis, an effect that was inhibited by blockade of the common CCL3/6/8 receptor CCR1. Further, Treg depletion unleashed pathologic CD4 T-cell responses. Our data point to new mechanisms regulating fibroblast differentiation in pancreatic cancer and support the notion that fibroblasts are a heterogeneous population with different and opposing functions in pancreatic carcinogenesis. SIGNIFICANCE: Here, we describe an unexpected cross-talk between Tregs and fibroblasts in pancreatic cancer. Treg depletion resulted in differentiation of inflammatory fibroblast subsets, in turn driving infiltration of myeloid cells through CCR1, thus uncovering a potentially new therapeutic approach to relieve immunosuppression in pancreatic cancer...
Topics: Animals; Carcinogenesis; Chemokine CCL3; Chemokine CCL8; Chemokines, CC; Disease Models, Animal; Fibroblasts; Humans; Mice; Pancreas; Pancreatic Neoplasms; Receptors, CCR1; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Tumor Microenvironment
PubMed: 31911451
DOI: 10.1158/2159-8290.CD-19-0958 -
Signal Transduction and Targeted Therapy Feb 2021Eosinophils are terminally differentiated cells derived from hematopoietic stem cells (HSCs) in the bone marrow. Several studies have confirmed the effective roles of...
Eosinophils are terminally differentiated cells derived from hematopoietic stem cells (HSCs) in the bone marrow. Several studies have confirmed the effective roles of eosinophils in asthmatic airway pathogenesis. However, their regulatory functions have not been well elucidated. Here, increased C-C chemokine ligand 6 (CCL6) in asthmatic mice and the human orthologs CCL15 and CCL23 that are highly expressed in asthma patients are described, which are mainly derived from eosinophils. Using Ccl6 knockout mice, further studies revealed CCL6-dependent allergic airway inflammation and committed eosinophilia in the bone marrow following ovalbumin (OVA) challenge and identified a CCL6-CCR1 regulatory axis in hematopoietic stem cells (HSCs). Eosinophil differentiation and airway inflammation were remarkably decreased by the specific CCR1 antagonist BX471. Thus, the study identifies that the CCL6-CCR1 axis is involved in the crosstalk between eosinophils and HSCs during the development of allergic airway inflammation, which also reveals a potential therapeutic strategy for targeting G protein-coupled receptors (GPCRs) for future clinical treatment of asthma.
Topics: Adolescent; Adult; Aged; Animals; Asthma; Bone Marrow; Cell Differentiation; Chemokines, CC; Eosinophils; Female; Healthy Volunteers; Hematopoietic Stem Cells; Humans; Hypersensitivity; Inflammation; Lung; Macrophage Inflammatory Proteins; Male; Mice; Mice, Knockout; Middle Aged; Ovalbumin; Phenylurea Compounds; Piperidines; Receptors, CCR1; Signal Transduction; Young Adult
PubMed: 33640900
DOI: 10.1038/s41392-021-00482-x -
Frontiers in Immunology 2023CCL13/MCP-4 belongs to the CC chemokine family, which induces chemotaxis in many immune cells. Despite extensive research into its function in numerous disorders, a... (Review)
Review
CCL13/MCP-4 belongs to the CC chemokine family, which induces chemotaxis in many immune cells. Despite extensive research into its function in numerous disorders, a thorough analysis of CCL13 is not yet accessible. The role of CCL13 in human disorders and existing CCL13-focused therapies are outlined in this study. The function of CCL13 in rheumatic diseases, skin conditions, and cancer is comparatively well-established, and some studies also suggest that it may be involved in ocular disorders, orthopedic conditions, nasal polyps, and obesity. We also give an overview of research that found very little evidence of CCL13 in HIV, nephritis, and multiple sclerosis. Even though CCL13-mediated inflammation is frequently linked to disease pathogenesis, it's fascinating to note that in some conditions, like primary biliary cholangitis (PBC) and suicide, it might even act as a preventative measure.
Topics: Humans; Chemokines, CC; Monocyte Chemoattractant Proteins
PubMed: 37153575
DOI: 10.3389/fimmu.2023.1176639