scholarly journals The CCL20-CCR6 Axis in Cancer Progression

2020 ◽  
Vol 21 (15) ◽  
pp. 5186 ◽  
Author(s):  
Suguru Kadomoto ◽  
Kouji Izumi ◽  
Atsushi Mizokami
Keyword(s):  
Cancer Progression ◽  
Immune Cell ◽  
G Protein Coupled Receptors ◽  
Virus Infections ◽  
Cancer Breast ◽  
Inflammatory Protein ◽  
Immunodeficiency Virus ◽  
G Protein Coupled ◽  
Macrophage Inflammatory Protein

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 C-C 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.

scholarly journals The Role of Endocrine G Protein-Coupled Receptors in Ovarian Cancer Progression

2017 ◽  
Vol 8 ◽  
Author(s):  
Qingyu Zhang ◽  
Nadine Ellen Madden ◽  
Alice Sze Tsai Wong ◽  
Billy Kwok Chong Chow ◽  
Leo Tsz On Lee
Keyword(s):  
Ovarian Cancer ◽  
G Protein ◽  
Cancer Progression ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

scholarly journals CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1706
Author(s):  
Chih-Lun Cheng ◽  
Shang-Chih Yang ◽  
Chien-Ying Lai ◽  
Cheng-Kai Wang ◽  
Ching-Fang Chang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Receptor Tyrosine Kinase ◽  
Cell Biology ◽  
Embryonic Stem ◽  
G Protein Coupled Receptors ◽  
Cell Cycle Distribution ◽  
Self Renewal ◽  
Inflammatory Protein ◽  
G Protein Coupled ◽  
Macrophage Inflammatory Protein

Human embryonic stem cells (hESCs) have important roles in regenerative medicine, but only a few studies have investigated the cytokines secreted by hESCs. We screened and identified chemokine (C-X-C motif) ligand 14 (CXCL14), which plays crucial roles in hESC renewal. CXCL14, a C-X-C motif chemokine, is also named as breast and kidney-expressed chemokine (BRAK), B cell and monocyte-activated chemokine (BMAC), and macrophage inflammatory protein-2γ (MIP-2γ). Knockdown of CXCL14 disrupted the hESC self-renewal, changed cell cycle distribution, and further increased the expression levels of mesoderm and endoderm differentiated markers. Interestingly, we demonstrated that CXCL14 is the ligand for the insulin-like growth factor 1 receptor (IGF-1R), and it can activate IGF-1R signal transduction to support hESC renewal. Currently published literature indicates that all receptors in the CXCL family are G protein-coupled receptors (GPCRs). This report is the first to demonstrate that a CXCL protein can bind to and activate a receptor tyrosine kinase (RTK), and also the first to show that IGF-1R has another ligand in addition to IGFs. These findings broaden our understanding of stem cell biology and signal transduction.

scholarly journals The pattern of immune cell infiltration in chromoblastomycosis: involvement of macrophage inflammatory protein-1 alpha/CCL3 and fungi persistence

2007 ◽  
Vol 49 (1) ◽  
pp. 49-53 ◽  
Author(s):  
Vanuza Cristina Sá ◽  
Tarcília Aparecida Silva ◽  
Carmelia Matos Santiago Reis ◽  
Fernando Queiroz Cunha ◽  
Florêncio Figueiredo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chemokine Receptors ◽  
Inflammatory Infiltrate ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Inflammatory Protein ◽  
Oxide Synthase ◽  
Macrophage Inflammatory Protein

Chromoblastomycosis (CR) is a subcutaneous chronic mycosis characterized by a granulomatous inflammatory response. However, little is known regarding the pattern of leukocyte subsets in CR and the pathways involved in their recruitment. The objective of this study was to assess the cellular subsets, chemokine, chemokine receptors and enzymes in CR. The inflammatory infiltrate was characterized by immunohistochemistry using antibodies against macrophages (CD68), Langerhans'cells (S100), lymphocytes (CD3, CD4, CD8, CD45RO, CD20 and CD56) and neutrophils (CD15). The expression of MIP-1alpha (Macrophage inflammatory protein-1alpha), chemokine receptors (CXCR3 and CCR1) and enzymes (superoxide dismutase-SOD and nitric oxide synthase-iNOS) was also evaluated by the same method. We observed an increase in all populations evaluated when compared with the controls. Numbers of CD15+ and CD56+ were significantly lower than CD3+, CD4+, CD20+ and CD68+ cells. Statistical analysis revealed an association of fungi numbers with CD3, CD45RO and iNOS-positive cells. Furthermore, MIP-1alpha expression was associated with CD45RO, CD68, iNOS and CXCR3. Our results suggest a possible role of MIP-1alpha and fungi persistence in the cell infiltration in CR sites.

scholarly journals Human Herpesvirus 7 Open Reading Frame U12 Encodes a Functional β-Chemokine Receptor

2003 ◽  
Vol 77 (14) ◽  
pp. 8108-8115 ◽  
Author(s):  
Kazushi Nakano ◽  
Kenjiro Tadagaki ◽  
Yuji Isegawa ◽  
Mya Mya Aye ◽  
Ping Zou ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Biological Function ◽  
Human Herpesvirus ◽  
G Protein Coupled Receptors ◽  
Biological Functions ◽  
Reading Frame ◽  
Inflammatory Protein ◽  
G Protein Coupled ◽  
Macrophage Inflammatory Protein

ABSTRACT Human herpesvirus 7 (HHV-7), which belongs to the betaherpesvirus subfamily, infects mainly CD4+ T cells in vitro and infects children during infancy. After the primary infection, HHV-7 becomes latent. HHV-7 contains two genes (U12 and U51) that encode putative homologs of cellular G-protein-coupled receptors. To analyze the biological function of the U12 gene, we cloned the gene and expressed the U12 protein in cells. The U12 gene encoded a calcium-mobilizing receptor for the EBI1 ligand chemokine-macrophage inflammatory protein 3β (ELC/MIP-3β) but not for other chemokines, suggesting that the chemokine selectivity of the U12 gene product is distinct from that of the known mammalian chemokine receptors. These studies revealed that U12 activates distinct transmembrane signaling pathways that may mediate biological functions by binding with a β-chemokine, ELC/MIP-3β.

Aggregation-independent modulation of proteoglycan binding by neutralization of C-terminal acidic residues in the chemokine macrophage inflammatory protein 1α

2001 ◽  
Vol 354 (2) ◽  
pp. 447-453 ◽  
Author(s):  
Katrin OTTERSBACH ◽  
Gerard J. GRAHAM
Keyword(s):  
Biological Effects ◽  
Biochemical Properties ◽  
Detectable Effect ◽  
Amino Acid Residues ◽  
Platelet Factor ◽  
Inflammatory Protein ◽  
G Protein Coupled ◽  
Macrophage Inflammatory Protein ◽  
Chemokine Family

Members of the chemokine family of proteins mediate their biological effects through interaction with a family of seven-transmembrane G-protein-coupled receptors. This interaction is complicated by the biochemical properties of chemokines, such as their ability to form self aggregates and their ability to bind to proteoglycans. With some chemokines there is a clear interrelationship between these interactions; the chemokine platelet factor 4 binds preferentially to proteoglycans in its aggregated form. Little is known about the role of aggregation in the proteoglycan binding of other chemokines. Here we demonstrate that the aggregation status of the chemokine macrophage inflammatory protein 1α (MIP-1α) has no detectable effect on its affinity for proteoglycans. Furthermore, we demonstrate that the alteration of acidic amino acid residues in MIP-1α influences the affinity of its interactions with heparin as these residues are progressively neutralized, leading to an enhanced binding affinity for heparin. Thus, with MIP-1α, aggregation is not a determinant of proteoglycan binding; however, overall charge does seem to have a major role in the interaction. These results therefore add to our understanding of the nature of the interaction between MIP-1α and proteoglycans and suggests that the basic amino acids might not be the sole regulators of proteoglycan binding.

Cholesterol is essential for macrophage inflammatory protein 1β binding and conformational integrity of CC chemokine receptor 5

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4298-4306 ◽  
Author(s):  
Dzung H. Nguyen ◽  
Dennis Taub
Keyword(s):  
Lipid Rafts ◽  
Chemokine Receptor ◽  
Membrane Microdomains ◽  
Inflammatory Protein ◽  
Immunodeficiency Virus ◽  
Chemokine Receptor Ccr5 ◽  
And Function ◽  
Cc Chemokine Receptor 5 ◽  
Macrophage Inflammatory Protein

The chemokine receptor, CCR5, is used as a human immunodeficiency virus coreceptor in combination with CD4 during transmission and early infection. CCR5 has been shown to be palmitoylated and targeted to cholesterol- and sphingolipid-rich membrane microdomains termed “lipid rafts.” However, the role of cholesterol and lipid rafts on chemokine binding and signaling through CCR5 remains unknown. We found that cholesterol extraction by hydroxypropyl-β-cyclodextrin (BCD) significantly reduced the binding and signaling of macrophage inflammatory protein 1β (MIP-1β) using CCR5-expressing CEM-NKR T cells. Reloading treated cells with cholesterol but not 4-cholesten-3-one, an oxidized form of cholesterol, restored MIP-1β binding to BCD-treated cells. Antibodies specific for distinct CCR5 epitopes lost their ability to bind to the cell surface after cholesterol extraction to varying degrees. Moreover, cells stained with fluorescently labeled MIP-1β extensively colocalized with the GM1 lipid raft marker while using anti-CCR5 antibodies; most of CCR5 on these cells only partially colocalized with GM1, suggesting that active ligand binding facilitates receptor association with lipid rafts or that raft association promotes a higher affinity conformation of CCR5. Together, these data demonstrate that cholesterol and lipid rafts are important for the maintenance of the CCR5 conformation and are necessary for both the binding and function of this chemokine receptor.

scholarly journals Granzyme B inhibition reduces disease severity in autoimmune blistering diseases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sho Hiroyasu ◽  
Matthew R. Zeglinski ◽  
Hongyan Zhao ◽  
Megan A. Pawluk ◽  
Christopher T. Turner ◽  
...  
Keyword(s):  
Immune Cell ◽  
Granzyme B ◽  
Neutrophil Infiltration ◽  
Inflammatory Protein ◽  
Anchoring Proteins ◽  
Macrophage Inflammatory Protein ◽  
Autoimmune Blistering Diseases

AbstractPemphigoid diseases refer to a group of severe autoimmune skin blistering diseases characterized by subepidermal blistering and loss of dermal-epidermal adhesion induced by autoantibody and immune cell infiltrate at the dermal-epidermal junction and upper dermis. Here, we explore the role of the immune cell-secreted serine protease, granzyme B, in pemphigoid disease pathogenesis using three independent murine models. In all models, granzyme B knockout or topical pharmacological inhibition significantly reduces total blistering area compared to controls. In vivo and in vitro studies show that granzyme B contributes to blistering by degrading key anchoring proteins in the dermal-epidermal junction that are necessary for dermal-epidermal adhesion. Further, granzyme B mediates IL-8/macrophage inflammatory protein-2 secretion, lesional neutrophil infiltration, and lesional neutrophil elastase activity. Clinically, granzyme B is elevated and abundant in human pemphigoid disease blister fluids and lesional skin. Collectively, granzyme B is a potential therapeutic target in pemphigoid diseases.

Carbazole Derivatives as Kinase-Targeting Inhibitors for Cancer Treatment

2020 ◽  
Vol 20 (6) ◽  
pp. 444-465 ◽  
Author(s):  
Jessica Ceramella ◽  
Domenico Iacopetta ◽  
Alexia Barbarossa ◽  
Anna Caruso ◽  
Fedora Grande ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Drug Targets ◽  
Mechanisms Of Action ◽  
Biological Pathways ◽  
G Protein Coupled Receptors ◽  
Ability To Act ◽  
Different Types ◽  
Activity Of Enzymes ◽  
Intercalating Agents ◽  
G Protein Coupled

Protein Kinases (PKs) are a heterogeneous family of enzymes that modulate several biological pathways, including cell division, cytoskeletal rearrangement, differentiation and apoptosis. In particular, due to their crucial role during human tumorigenesis and cancer progression, PKs are ideal targets for the design and development of effective and low toxic chemotherapeutics and represent the second group of drug targets after G-protein-coupled receptors. Nowadays, several compounds have been claimed to be PKs inhibitors, and some of them, such as imatinib, erlotinib and gefitinib, have already been approved for clinical use, whereas more than 30 others are in various phases of clinical trials. Among them, some natural or synthetic carbazole-based molecules represent promising PKs inhibitors due to their capability to interfere with PK activity by different mechanisms of action including the ability to act as DNA intercalating agents, interfere with the activity of enzymes involved in DNA duplication, such as topoisomerases and telomerases, and inhibit other proteins such as cyclindependent kinases or antagonize estrogen receptors. Thus, carbazoles can be considered a promising this class of compounds to be adopted in targeted therapy of different types of cancer.

Recent Advances of Small Molecular Regulators Targeting G Protein- Coupled Receptors Family for Oncology Immunotherapy

2019 ◽  
Vol 19 (16) ◽  
pp. 1464-1483 ◽  
Author(s):  
Peng He ◽  
Wenbo Zhou ◽  
Mingyao Liu ◽  
Yihua Chen
Keyword(s):  
G Protein ◽  
Cell Biology ◽  
Immune Cell ◽  
G Protein Coupled Receptors ◽  
Treatment Modalities ◽  
Immune Checkpoints ◽  
Considerable Proportion ◽  
Prostaglandin E ◽  
Recent Advances ◽  
G Protein Coupled

The great clinical success of chimeric antigen receptor T cell (CAR-T) and PD-1/PDL-1 inhibitor therapies suggests the drawing of a cancer immunotherapy age. However, a considerable proportion of cancer patients currently receive little benefit from these treatment modalities, indicating that multiple immunosuppressive mechanisms exist in the tumor microenvironment. In this review, we mainly discuss recent advances in small molecular regulators targeting G Protein-Coupled Receptors (GPCRs) that are associated with oncology immunomodulation, including chemokine receptors, purinergic receptors, prostaglandin E receptor EP4 and opioid receptors. Moreover, we outline how they affect tumor immunity and neoplasia by regulating immune cell recruitment and modulating tumor stromal cell biology. We also summarize the data from recent clinical advances in small molecular regulators targeting these GPCRs, in combination with immune checkpoints blockers, such as PD-1/PDL-1 and CTLA4 inhibitors, for cancer treatments.

scholarly journals Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Neil N. Patel ◽  
Alan D. Workman ◽  
Noam A. Cohen
Keyword(s):  
Airway Epithelium ◽  
Taste Receptor ◽  
Upper Airway ◽  
Airway Disease ◽  
G Protein Coupled Receptors ◽  
Innate Immune ◽  
Taste Receptors ◽  
Taste Sensation ◽  
G Protein Coupled

Evidence is emerging that shows taste receptors serve functions outside of taste sensation of the tongue. Taste receptors have been found in tissue across the human body, including the gastrointestinal tract, bladder, brain, and airway. These extraoral taste receptors appear to be important in modulating the innate immune response through detection of pathogens. This review discusses taste receptor signaling, focusing on the G-protein–coupled receptors that detect bitter and sweet compounds in the upper airway epithelium. Emphasis is given to recent studies which link the physiology of sinonasal taste receptors to clinical manifestation of upper airway disease.

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