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Life
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Chemokines and Their Receptors
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Chemokines and Their Receptors

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (21 June 2021) | Viewed by 16390

Special Issue Editors

Dr. Olga M. Koper-Lenkiewicz

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Guest Editor
Department of Clinical Laboratory Diagnostics, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, 15-089 Białystok, Poland
Interests: cerebrospinal fluid; biomarker; central nervous system diseases
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Violetta Dymicka-Piekarska

E-Mail Website
Guest Editor
Department of Clinical Laboratory Diagnostics, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, 15-089 Białystok, Poland
Interests: cancer immunology and biomarkers; cardiovascular diseases; inflammation; platelets; thrombosis
Dr. Joanna Kamińska

E-Mail Website
Guest Editor
Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland
Interests: cancer; central nervous system diseases; cerebrospinal fluid; cytokines; biomarker; inflammation markers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chemokines are small proteins that play a crucial role in the migration of immunocompetent cells to inflammation sites. They were originally discovered by their leukocyte adhesion, chemotaxis, and activation abilities, both in vivo and in vitro. Chemokines are also involved in immune surveillance and are able to direct B or T lymphocytes towards the antigen. Chemokines may be potentially useful as therapeutic targets. Moreover, chemokines act via G-protein-coupled receptors, which are the most common targets of the modern therapeutic strategy widely reaching various clinics.

We call for original papers, reviews, and other forms of scientific communication providing new findings regarding the role of chemokines and their receptors in the pathophysiology and diagnosis of diseases. Studies concerning genetic and mRNA splice variants of chemokines and their receptors are also welcomed. Human studies are preferred.

Dr. Olga M. Koper-Lenkiewicz
Prof. Dr. Violetta Dymicka-Piekarska
Dr. Joanna Kamińska
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chemokines
  • chemokines receptors
  • inflammation
  • disease state
  • gene polymorphisms
  • mRNA splice variants

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Published Papers (5 papers)

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Research

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12 pages, 1692 KiB  
Article
Monocyte Chemotactic Proteins Mediate the Effects of Hyperglycemia in Chondrocytes: In Vitro Studies
by Adam Quincey, Subburaman Mohan and Bouchra Edderkaoui
Life 2022, 12(6), 836; https://doi.org/10.3390/life12060836 - 3 Jun 2022
Cited by 3 | Viewed by 1812
Abstract
Chemokines are secreted by a large variety of cells. They are involved in controlling cell trafficking, maturation, and differentiation. However, the specific responses and effects of chemokines on specific skeletal cell types under high glucose conditions have not been investigated. Chondrocytes play an [...] Read more.
Chemokines are secreted by a large variety of cells. They are involved in controlling cell trafficking, maturation, and differentiation. However, the specific responses and effects of chemokines on specific skeletal cell types under high glucose conditions have not been investigated. Chondrocytes play an important role in osteoarthritis and fracture healing. Delayed fracture healing is one of the major health complications caused by diabetes, so the goal of this study was to evaluate the response of several chemokines to high glucose conditions in chondrocyte cells and analyze their role in the catabolic effect of hyperglycemia. ATDC5 chondrocytes were cultured in normal and high glucose media, and mRNA expression levels of several chemokines and chondrocyte differentiation markers were quantified. Bindarit, a specific inhibitor of monocyte chemotactic proteins (MCPs), was used to determine the role of MCPs in mediating the effects of high glucose conditions in chondrocyte cells. High glucose treatment upregulated the expression of three Mcps, as well as the expression of matrix metalloproteinase 13 (Mmp13) and Osteocalcin (Oc). Furthermore, bindarit treatment downregulated Mmp13 and Oc but upregulated Collagen 2 (Col2) mRNA levels in chondrocytes treated with high glucose. Moreover, treatment of chondrocytes with ascorbic acid reduced the effect of high glucose conditions on the expression of chemokines and Mmps. These data together suggest that MCPs mediate the catabolic effect of high glucose in chondrocytes. Full article
(This article belongs to the Special Issue Chemokines and Their Receptors)
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15 pages, 5310 KiB  
Article
Monocyte Chemotactic Protein-1 (MCP1) Accumulation in Human Osteoclast Precursor Cultures
by Nigel A. Morrison and Mark R. Forwood
Life 2022, 12(6), 789; https://doi.org/10.3390/life12060789 - 26 May 2022
Cited by 4 | Viewed by 2071
Abstract
In vitro osteoclast methods require constant treatment with macrophage colony stimulating factor (M-CSF) to support precursor survival and addition of the differentiation agent receptor activator of NF-κB ligand (RANKL). Constant exposure to granulocyte macrophage colony stimulating factor (GM-CSF) suppresses human osteoclast formation in [...] Read more.
In vitro osteoclast methods require constant treatment with macrophage colony stimulating factor (M-CSF) to support precursor survival and addition of the differentiation agent receptor activator of NF-κB ligand (RANKL). Constant exposure to granulocyte macrophage colony stimulating factor (GM-CSF) suppresses human osteoclast formation in vitro. Addition of the chemokine monocyte chemotactic protein-1 (MCP1) to such cultures dramatically increases osteoclast formation and overcomes GM-CSF mediated suppression. We investigated the effect of M-CSF, GM-CSF and the combination of M-CSF and GM-CSF treatment on the expression of chemokines in human CD14+ cells in culture. Of assayed chemokines, MCP1 was the most abundant in terms of mRNA transcript and protein in M-CSF treated cultures and was suppressed by GM-CSF. MCP1 protein accumulated up to 50 ng/mL in culture medium, greatly exceeding other assayed chemokines. C-C chemokine receptor-2 (CCR2) is the receptor for MCP1: the formation of osteoclast-like cells was inhibited by constant exposure to the CCR2 antagonist RS102895, in part by decreasing expression of RANK, the receptor for RANKL. Full article
(This article belongs to the Special Issue Chemokines and Their Receptors)
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18 pages, 3407 KiB  
Article
CXCR4-CCR7 Heterodimerization Is a Driver of Breast Cancer Progression
by Valentina Poltavets, Jessica W. Faulkner, Deepak Dhatrak, Robert J. Whitfield, Shaun R. McColl and Marina Kochetkova
Life 2021, 11(10), 1049; https://doi.org/10.3390/life11101049 - 7 Oct 2021
Cited by 6 | Viewed by 3821
Abstract
Metastatic breast cancer has one of the highest mortality rates among women in western society. Chemokine receptors CXCR4 and CCR7 have been shown to be linked to the metastatic spread of breast cancer, however, their precise function and underlying molecular pathways leading to [...] Read more.
Metastatic breast cancer has one of the highest mortality rates among women in western society. Chemokine receptors CXCR4 and CCR7 have been shown to be linked to the metastatic spread of breast cancer, however, their precise function and underlying molecular pathways leading to the acquisition of the pro-metastatic properties remain poorly understood. We demonstrate here that the CXCR4 and CCR7 receptor ligands, CXCL12 and CCL19, cooperatively bind and selectively elicit synergistic signalling responses in invasive breast cancer cell lines as well as primary mammary human tumour cells. Furthermore, for the first time, we have documented the presence of CXCR4-CCR7 heterodimers in advanced primary mammary mouse and human tumours where number of CXCR4-CCR7 complexes directly correlate with the severity of the disease. The functional significance of the CXCR4-CCR7 association was also demonstrated when their forced heterodimerization led to the acquisition of invasive phenotype in non-metastatic breast cancer cells. Taken together, our data establish the CXCR4-CCR7 receptor complex as a new functional unit, which is responsible for the acquisition of breast cancer cell metastatic phenotype and which may serve as a novel biomarker for invasive mammary tumours. Full article
(This article belongs to the Special Issue Chemokines and Their Receptors)
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14 pages, 5268 KiB  
Article
CXCR3 Expression and Genome-Wide 3′ Splice Site Selection in the TCGA Breast Cancer Cohort
by Lauren A. Levesque, Scott Roy and Nicole Salazar
Life 2021, 11(8), 746; https://doi.org/10.3390/life11080746 - 26 Jul 2021
Cited by 3 | Viewed by 3595
Abstract
CXCR3 is a chemokine receptor with two well-characterized isoforms that have unique, context-dependent roles: CXCR3-A and CXCR3-B, which are produced through alternative 3′ splice site selection (A3SS). RNA-seq data from The Cancer Genome Atlas (TCGA) were used to correlate CXCR3 expression with breast [...] Read more.
CXCR3 is a chemokine receptor with two well-characterized isoforms that have unique, context-dependent roles: CXCR3-A and CXCR3-B, which are produced through alternative 3′ splice site selection (A3SS). RNA-seq data from The Cancer Genome Atlas (TCGA) were used to correlate CXCR3 expression with breast cancer progression. This analysis revealed significant CXCR3 expression patterns associated with survival and differential expression between the tumor and adjacent normal tissue. TCGA data were used to estimate abundance of immune cells in breast cancer, which demonstrated the association of CXCR3 with immune infiltration, particularly in the triple-negative subtype. Given the importance of A3SS in CXCR3, genome-wide analysis of A3SS events was performed to identify events that were differentially spliced between breast cancer tissue and adjacent normal tissue. A total of 481 splicing events in 424 genes were found to be differentially spliced. The parent genes of differentially spliced events were enriched in RNA processing and splicing functions, indicating an underappreciated role of A3SS in the integrated splicing network of breast cancer. These results further validated the role of CXCR3 in immune infiltration of tumors, while raising questions about the role of A3SS splicing. Full article
(This article belongs to the Special Issue Chemokines and Their Receptors)
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Review

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21 pages, 1694 KiB  
Review
Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection
by Marina Alves Fontoura, Rebeca Fróes Rocha and Rafael Elias Marques
Life 2021, 11(7), 717; https://doi.org/10.3390/life11070717 - 20 Jul 2021
Cited by 2 | Viewed by 3742
Abstract
Neutrophils are first-line responders to infections and are recruited to target tissues through the action of chemoattractant molecules, such as chemokines. Neutrophils are crucial for the control of bacterial and fungal infections, but their role in the context of viral infections has been [...] Read more.
Neutrophils are first-line responders to infections and are recruited to target tissues through the action of chemoattractant molecules, such as chemokines. Neutrophils are crucial for the control of bacterial and fungal infections, but their role in the context of viral infections has been understudied. Flaviviruses are important human viral pathogens transmitted by arthropods. Infection with a flavivirus may result in a variety of complex disease manifestations, including hemorrhagic fever, encephalitis or congenital malformations. Our understanding of flaviviral diseases is incomplete, and so is the role of neutrophils in such diseases. Here we present a comprehensive overview on the participation of neutrophils in severe disease forms evolving from flavivirus infection, focusing on the role of chemokines and their receptors as main drivers of neutrophil function. Neutrophil activation during viral infection was shown to interfere in viral replication through effector functions, but the resulting inflammation is significant and may be detrimental to the host. For congenital infections in humans, neutrophil recruitment mediated by CXCL8 would be catastrophic. Evidence suggests that control of neutrophil recruitment to flavivirus-infected tissues may reduce immunopathology in experimental models and patients, with minimal loss to viral clearance. Further investigation on the roles of neutrophils in flaviviral infections may reveal unappreciated functions of this leukocyte population while increasing our understanding of flaviviral disease pathogenesis in its multiple forms. Full article
(This article belongs to the Special Issue Chemokines and Their Receptors)
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