-
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 -
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 -
Cancer Cell Apr 2011Tumor-associated macrophages (TAMs) can influence cancer progression and metastasis, but the mechanism remains unclear. Here, we show that breast TAMs abundantly produce...
Tumor-associated macrophages (TAMs) can influence cancer progression and metastasis, but the mechanism remains unclear. Here, we show that breast TAMs abundantly produce CCL18, and its expression in blood or cancer stroma is associated with metastasis and reduced patient survival. CCL18 released by breast TAMs promotes the invasiveness of cancer cells by triggering integrin clustering and enhancing their adherence to extracellular matrix. Furthermore, we identify PITPNM3 as a functional receptor for CCL18 that mediates CCL18 effect and activates intracellular calcium signaling. CCL18 promotes the invasion and metastasis of breast cancer xenografts, whereas suppressing PITPNM3 abrogates these effects. These findings indicate that CCL18 derived from TAMs plays a critical role in promoting breast cancer metastasis via its receptor, PITPNM3.
Topics: Adult; Aged; Breast Neoplasms; Calcium-Binding Proteins; Cell Adhesion; Cell Line, Tumor; Cell Movement; Chemokines, CC; Female; Humans; Interleukin-4; Macrophages; Membrane Proteins; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; RNA, Messenger
PubMed: 21481794
DOI: 10.1016/j.ccr.2011.02.006 -
Arthritis Research & Therapy Jul 2023Osteoarthritis (OA) is a prevalent degenerative disease accompanied by the activation of innate and adaptive immune systems-associated inflammatory responses. Due to the... (Review)
Review
Osteoarthritis (OA) is a prevalent degenerative disease accompanied by the activation of innate and adaptive immune systems-associated inflammatory responses. Due to the local inflammation, the expression of various cytokines was altered in affected joints, including CC motif chemokine ligands (CCLs) and their receptors (CCRs). As essential members of chemokines, CCLs and CCRs played an important role in the pathogenesis and treatment of OA. The bindings between CCLs and CCRs on the chondrocyte membrane promoted chondrocyte apoptosis and the release of multiple matrix-degrading enzymes, which resulted in cartilage degradation. In addition, CCLs and CCRs had chemoattractant functions to attract various immune cells to osteoarthritic joints, further leading to the aggravation of local inflammation. Furthermore, in the nerve endings of joints, CCLs and CCRs, along with several cellular factors, contributed to pain hypersensitivity by releasing neurotransmitters in the spinal cord. Given this family's diverse and complex functions, targeting the functional network of CCLs and CCRs is a promising strategy for the prognosis and treatment of OA in the future.
Topics: Humans; Chemokines, CC; Cartilage, Articular; Osteoarthritis; Chemokines; Inflammation; Chondrocytes
PubMed: 37400871
DOI: 10.1186/s13075-023-03096-6 -
International Journal of Molecular... Oct 2020A neoplastic tumor consists of cancer cells that interact with each other and non-cancerous cells that support the development of the cancer. One such cell are... (Review)
Review
A neoplastic tumor consists of cancer cells that interact with each other and non-cancerous cells that support the development of the cancer. One such cell are tumor-associated macrophages (TAMs). These cells secrete many chemokines into the tumor microenvironment, including especially a large amount of CCL18. This chemokine is a marker of the M2 macrophage subset; this is the reason why an increase in the production of CCL18 is associated with the immunosuppressive nature of the tumor microenvironment and an important element of cancer immune evasion. Consequently, elevated levels of CCL18 in the serum and the tumor are connected with a worse prognosis for the patient. This paper shows the importance of CCL18 in neoplastic processes. It includes a description of the signal transduction from PITPNM3 in CCL18-dependent migration, invasion, and epithelial-to-mesenchymal transition (EMT) cancer cells. The importance of CCL18 in angiogenesis has also been described. The paper also describes the effect of CCL18 on the recruitment to the cancer niche and the functioning of cells such as TAMs, regulatory T cells (T), cancer-associated fibroblasts (CAFs) and tumor-associated dendritic cells (TADCs). The last part of the paper describes the possibility of using CCL18 as a therapeutic target during anti-cancer therapy.
Topics: Calcium-Binding Proteins; Cancer-Associated Fibroblasts; Chemokines, CC; Disease Progression; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Macrophages; Membrane Proteins; Neoplasms; Prognosis; Tumor Escape; Tumor Microenvironment; Up-Regulation
PubMed: 33114763
DOI: 10.3390/ijms21217955 -
Biomolecules Feb 2023Idiopathic pulmonary fibrosis (IPF), characterized by progressive worsening of dyspnea and irreversible decline in lung function, is a chronic and progressive... (Review)
Review
Idiopathic pulmonary fibrosis (IPF), characterized by progressive worsening of dyspnea and irreversible decline in lung function, is a chronic and progressive respiratory disease with a poor prognosis. Chronic or repeated lung injury results in inflammation and an excessive injury-repairing response that drives the development of IPF. A number of studies have shown that the development and progression of IPF are associated with dysregulated expression of several chemokines and chemokine receptors, several of which have been used as predictors of IPF outcome. Chemokines of the CC family play significant roles in exacerbating IPF progression by immune cell attraction or fibroblast activation. Modulating levels of detrimental CC chemokines and interrupting the corresponding transduction axis by neutralizing antibodies or antagonists are potential treatment options for IPF. Here, we review the roles of different CC chemokines in the pathogenesis of IPF, and their potential use as biomarkers or therapeutic targets.
Topics: Humans; Chemokines, CC; Idiopathic Pulmonary Fibrosis; Lung; Chemokines; Inflammation; Fibroblasts
PubMed: 36830702
DOI: 10.3390/biom13020333 -
Virology Journal Jun 2021It has been reported that polyomaviruses are the microbes which can be a cause of several human pathological conditions including cancers, nephropathy, progressive... (Review)
Review
It has been reported that polyomaviruses are the microbes which can be a cause of several human pathological conditions including cancers, nephropathy, progressive multifocal leukoencephalopathy and gynaecological disease. Although investigators proposed some mechanisms used by the viruses to induce the disorders, the roles played by chemokines in the pathogenesis of polyomaviruses infections are yet to be clarified. This review article investigated recent studies regarding the roles played by chemokines in the pathogenesis of the polyomaviruses infections. The research in the literature revealed that CXC chemokines, including CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12 and CXCL16, significantly participate in the pathogenesis of polyomaviruses. CC chemokines, such as CCL2, CCL5 and CCL20 also participate in the induction of the pathological conditions. Therefore, it appears that CXC chemokines may be considered as the strategic factors involved in the pathogenesis of polyomaviruses.
Topics: Chemokines, CC; Chemokines, CXC; Humans; Polyomavirus; Polyomavirus Infections
PubMed: 34082771
DOI: 10.1186/s12985-021-01582-4 -
International Journal of Infectious... Sep 2010Despite advances in neonatal care, sepsis remains a threat, in particular for premature neonates, due to immature immunologic defense. Deficient chemotaxis, an essential...
BACKGROUND
Despite advances in neonatal care, sepsis remains a threat, in particular for premature neonates, due to immature immunologic defense. Deficient chemotaxis, an essential process in the host response to pathogens, may contribute to this vulnerability. In this study we investigated chemokine expression in septic premature and term neonates.
METHODS
Seventy-one neonates with signs and symptoms suggestive of systemic infection, requiring full sepsis evaluation and treatment, formed the study group; 58 neonates without sepsis served as the control group. Serum concentrations of two α-chemokines (GRO-α and ENA-78) and two β-chemokines (RANTES and MIP-1α) were measured at day 0 and day 3-5 of infection in the study group, and on the day of inclusion in the study in the control group.
RESULTS
During infection, serum levels of GRO-α in the study group were higher and serum levels of RANTES were lower as compared to those of the control group (p<0.001 and p<0.001, respectively). Furthermore, levels of GRO-α were higher and levels of RANTES were lower on day 0 as compared to levels on day 3-5 (p<0.001 and p<0.001, respectively). Chemokine serum concentrations on day 3-5 in the study group did not differ significantly as compared to those of the control group. Term and preterm infants seemed to respond similarly regarding chemokine expression. No significant differences were found in serum levels of MIP-1α and ENA-78.
CONCLUSIONS
Our findings suggest up-regulation of GRO-α and down-regulation of RANTES at the onset of a septic episode, similar to the response pattern observed in septic adults. Both term and preterm neonates appear to have the potential to elicit a chemotactic response to infection.
Topics: Chemokine CCL5; Chemokine CXCL1; Chemokines, CC; Chemokines, CXC; Down-Regulation; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Sepsis; Up-Regulation
PubMed: 20685145
DOI: 10.1016/j.ijid.2010.03.015 -
European Cytokine Network 2001Monocyte chemotactic protein-3 (MCP-3) belongs to the MCP subgroup of CC chemokines that are structurally closely related but, which differ in receptor usage and hence... (Review)
Review
Monocyte chemotactic protein-3 (MCP-3) belongs to the MCP subgroup of CC chemokines that are structurally closely related but, which differ in receptor usage and hence in biological activities. MCP-3 is one of the most pluripotent chemokines since it activates all types of leukocytes, by binding to at least four different chemokine receptors. The natural protein is heterogeneous due to glycosylation and NH2-terminal processing. Only small amounts of MCP-3 are induced in various cell types by endogeneous (cytokines) or exogeneous (bacteria, viruses) agents. Nevertheless, this omnipotent chemokine, inducible in most body compartments, might play an important role in normal homeostasis as well as in various pathologies including cancer, auto-immune diseases and chronic inflammation.
Topics: Amino Acid Sequence; Animals; Chemokine CCL7; Cytokines; Humans; Molecular Sequence Data; Monocyte Chemoattractant Proteins; Sequence Homology, Amino Acid
PubMed: 11781181
DOI: No ID Found -
Frontiers in Immunology 2020Chemokines are essential for guiding cell migration. Atypical chemokine receptors (ACKRs) contribute to the cell migration process by binding, internalizing and...
Chemokines are essential for guiding cell migration. Atypical chemokine receptors (ACKRs) contribute to the cell migration process by binding, internalizing and degrading local chemokines, which enables the formation of confined gradients. ACKRs are heptahelical membrane spanning molecules structurally related to G-protein coupled receptors (GPCRs), but seem to be unable to signal through G-proteins upon ligand binding. ACKR4 internalizes the chemokines CCL19, CCL21, and CCL25 and is best known for shaping functional CCL21 gradients. Ligand binding to ACKR4 has been shown to recruit β-arrestins that has led to the assumption that chemokine scavenging relies on β-arrestin-mediated ACKR4 trafficking, a common internalization route taken by class A GPCRs. Here, we show that CCL19, CCL21, and CCL25 readily recruited β-arrestin1 and β-arrestin2 to human ACKR4, but found no evidence for β-arrestin-dependent or independent ACKR4-mediated activation of the kinases Erk1/2, Akt, or Src. However, we demonstrate that β-arrestins interacted with ACKR4 in the steady-state and contributed to the spontaneous trafficking of the receptor in the absence of chemokines. Deleting the C-terminus of ACKR4 not only interfered with the interaction of β-arrestins, but also with the uptake of fluorescently labeled cognate chemokines. We identify the GPCR kinase GRK3, and to a lesser extent GRK2, but not GRK4, GRK5, and GRK6, to be recruited to chemokine-stimulated ACKR4. We show that GRK3 recruitment proceded the recruitment of β-arrestins upon ACKR4 engagement and that GRK2/3 inhibition partially interfered with steady-state interaction and chemokine-driven recruitment of β-arrestins to ACKR4. Overexpressing β-arrestin2 accelerated the uptake of fluorescently labeled CCL19, indicating that β-arrestins contribute to the chemokine scavenging activity of ACKR4. By contrast, cells lacking β-arrestins were still capable to take up fluorescently labeled CCL19 demonstrating that β-arrestins are dispensable for chemokine scavenging by ACKR4.
Topics: Chemokine CCL19; Chemokine CCL21; Chemokines, CC; G-Protein-Coupled Receptor Kinase 3; HeLa Cells; Humans; Plasmids; Protein Binding; Receptors, CCR; Receptors, CCR7; Signal Transduction; Transfection; beta-Arrestin 1; beta-Arrestin 2
PubMed: 32391018
DOI: 10.3389/fimmu.2020.00720