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Brazilian Oral Research 2019Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions....
Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions. Regulatory (Treg) and Th17 cytokines play a key role in regulating the immune response involved in this process. The aim of this study was to investigate the role of Treg and Th17 cells in chronic inflammatory periapical disease, by comparing the expression of the immunoregulatory mediators TGF-β, IL-10, CCL4, and the proinflammatory IL-17 and CCL20 in the periapical tissue of teeth with pulp necrosis, with and without associated chronic lesions. Eighty-six periapical tissue samples were obtained from human teeth. The samples were divided into three groups: pulp necrosis with a periapical lesion (n=26); pulp necrosis without a periapical lesion (n=30), and control (n=30). All samples were submitted to histopathological analysis and cytokine and chemokine measurement through ELISA. Statistical analyses were done with Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. The group with pulp necrosis and a periapical lesion showed a higher expression of CCL4 and TGF-β in comparison with pulp necrosis without a lesion. CCL20 was higher in the group with a periapical lesion when compared to the control. In all groups there was a weak positive correlation between IL-17/CCL20, IL-10/CCL4, and IL-17/TGF-β. Both types of cytokines, pro-inflammatory and immunoregulatory, occur simultaneously in periapical tissue. However, a rise in immunosuppressive cytokines and chemokines (CCL4 and TGF-β) in periapical lesions suggests a role of these cytokines in stable periapical disease.
Topics: Adult; Case-Control Studies; Chemokines, CC; Chronic Disease; Dental Pulp Necrosis; Humans; Interleukins; Middle Aged; Periapical Periodontitis; Reference Values; Statistics, Nonparametric; T-Lymphocytes, Regulatory; Th17 Cells; Transforming Growth Factor beta; Young Adult
PubMed: 31664358
DOI: 10.1590/1807-3107bor-2019.vol33.0093 -
International Immunopharmacology Oct 2017Chemokines are an extensive family of small proteins which, in conjunction with their receptors, guide the chemotactic activity of various immune cells throughout the... (Review)
Review
Chemokines are an extensive family of small proteins which, in conjunction with their receptors, guide the chemotactic activity of various immune cells throughout the body. CCL28, β- or CC chemokine, is involved in the host immunity at various epithelial and mucosal linings. The unique roles of CCL28 in several facets of immune responses have attracted considerable attention and may represent a promising approach to combat various infections. CCL28 displays a broad spectrum of antimicrobial activity against gram-negative and gram-positive bacteria, as well as fungi. Here, we will summarize various research findings regarding the antimicrobial activity of CCL28 and the relevant mechanisms behind it. We will explore how the structure of CCL28 is involved with this activity and how this function may have evolved. CCL28 displays strong homing capabilities for B and T cells at several mucosal and epithelial sites, and orchestrates the trafficking and functioning of lymphocytes. The chemotactic and immunomodulatory features of CCL28 through the interactions with its chemokine receptors, CCR10 and CCR3, will also be discussed in detail. Thus, in this review, we emphasize the dual properties of CCL28 and suggest its role as an anchoring point bridging the innate and adaptive immunity.
Topics: Adaptive Immunity; Animals; Anti-Infective Agents; Cell Movement; Chemokines, CC; Chemotaxis; Humans; Immunity, Innate; Lymphocytes; Mucous Membrane
PubMed: 28843907
DOI: 10.1016/j.intimp.2017.08.012 -
PloS One 2018Being generally regarded as commensal bacteria, the pro-inflammatory capacity of Ureaplasma species has long been debated. Recently, we confirmed Ureaplasma-driven...
Being generally regarded as commensal bacteria, the pro-inflammatory capacity of Ureaplasma species has long been debated. Recently, we confirmed Ureaplasma-driven pro-inflammatory cytokine responses and a disturbance of cytokine equilibrium in primary human monocytes in vitro. The present study addressed the expression of CC chemokines and matrix metalloproteinase-9 (MMP-9) in purified term neonatal and adult monocytes stimulated with serovar 8 of Ureaplasma urealyticum (Uu) and serovar 3 of U. parvum (Up). Using qRT-PCR and multi-analyte immunoassay, we assessed mRNA and protein expression of the monocyte chemotactic proteins 1 and 3 (MCP-1/3), the macrophage inflammatory proteins 1α and 1β (MIP-1α/β) as well as MMP-9. For the most part, both isolates stimulated mRNA expression of all given chemokines and MMP-9 in cord blood and adult monocytes (p<0.05 and p<0.01). These results were paralleled by Uu and Up-induced secretion of MCP-1 protein in both cells (neonatal: p<0.01, adult: p<0.05 and p<0.01). Release of MCP-3, MIP-1α, MIP-1β and MMP-9 was enhanced upon exposure to Up (neonatal: p<0.05, p<0.01 and p<0.001, respectively; adult: p<0.05). Co-stimulation of LPS-primed monocytes with Up increased LPS-induced MCP-1 release in neonatal cells (p<0.05) and aggravated LPS-induced MMP-9 mRNA in both cell subsets (neonatal: p<0.05, adult: p<0.01). Our results document considerable expression of pro-inflammatory CC chemokines and MMP-9 in human monocytes in response to Ureaplasma isolates in vitro, adding to our previous data. Findings from co-stimulated cells indicate that Ureaplasma may modulate monocyte immune responses to a second stimulus.
Topics: Adult; Cells, Cultured; Chemokines, CC; Escherichia coli; Fetal Blood; Humans; Immunity, Cellular; Infant, Newborn; Lipopolysaccharides; Matrix Metalloproteinase 9; Monocytes; RNA, Messenger; Ureaplasma urealyticum; Urinary Tract Infections
PubMed: 29558521
DOI: 10.1371/journal.pone.0194514 -
Infection and Immunity Apr 2002Chemokines (CK) are potent leukocyte activators and chemoattractants and aid in granuloma formation, functions critical for the immune response to Mycobacterium...
Chemokines (CK) are potent leukocyte activators and chemoattractants and aid in granuloma formation, functions critical for the immune response to Mycobacterium tuberculosis. We hypothesized that infection of alveolar macrophages (AM) with different strains of M. tuberculosis elicits distinct profiles of CK, which could be altered by human immunodeficiency virus (HIV) infection. RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were the major beta-CK produced in response to M. tuberculosis infection. Virulent M. tuberculosis (H37Rv) induced significantly less MIP-1 alpha than did the avirulent strain (H37Ra), while MIP-1 beta and RANTES production was comparable for both strains. MIP-1 alpha and MIP-1 beta were induced by the membrane, but not cytosolic, fraction of M. tuberculosis. M. tuberculosis-induced CK secretion was partly dependent on tumor necrosis factor alpha (TNF-alpha). AM from HIV-infected individuals produced less TNF-alpha and MIP-1 beta than did normal AM in response to either M. tuberculosis strain. We tested the functional significance of decreased beta-CK secretion by examining the ability of beta-CK to suppress intracellular growth of M. tuberculosis. MIP-1 beta and RANTES suppressed intracellular growth of M. tuberculosis two- to threefold, a novel finding. Thus, beta-CK contribute to the innate immune response to M. tuberculosis infection, and their diminution may promote the intracellular survival of M. tuberculosis.
Topics: Chemokine CCL4; Chemokine CCL5; Chemokines, CC; Humans; Macrophage Inflammatory Proteins; Macrophages, Alveolar; Mycobacterium tuberculosis; Tumor Necrosis Factor-alpha
PubMed: 11895930
DOI: 10.1128/IAI.70.4.1684-1693.2002 -
The Journal of Biological Chemistry Aug 2008CXC and CC chemokines are involved in numerous biological processes, and their function in situ may be significantly influenced by heterodimer formation, as was recently...
CXC and CC chemokines are involved in numerous biological processes, and their function in situ may be significantly influenced by heterodimer formation, as was recently reported, for example, for CXC chemokines CXCL4/PF4 and CXCL8/IL8 that interact to form heterodimers that modulate chemotactic and cell proliferation activities. Here we used molecular dynamics simulations to determine relative association free energies (overall average and per residue) for homo- and heterodimer pairs of CXC (CXCL4/PF4, CXCL8/IL8, CXCL1/Gro-alpha, and CXCL7/NAP-2) and CC (CCL5/RANTES, CCL2/MCP-1, and CCL8/MCP-2) chemokines. Even though structural homology among monomer folds of all CXC and CC chemokines permits heterodimer assembly, our calculated association free energies depend upon the particular pair of chemokines in terms of the net electrostatic and nonelectrostatic forces involved, as well as (for CC/CXC mixed chemokines) the selection of dimer type (CC or CXC). These relative free energies indicate that association of some pairs of chemokines is more favorable than others. Our approach is validated by correlation of calculated and experimentally determined free energies. Results are discussed in terms of CXC and CC chemokine function and have significant biological implications.
Topics: Animals; Chemokines, CC; Chemokines, CXC; Computer Simulation; Dimerization; Humans; Static Electricity; Thermodynamics
PubMed: 18550532
DOI: 10.1074/jbc.M803308200 -
European Surgical Research. Europaische... 2022The present research set out to ascertain the roles of CC chemokine ligand 21 (CCL21) and cystathionine beta-synthase (CBS) in breast cancer (BC) cell biological...
OBJECTIVE
The present research set out to ascertain the roles of CC chemokine ligand 21 (CCL21) and cystathionine beta-synthase (CBS) in breast cancer (BC) cell biological behaviors and the relationship of CCL21 and CBS expression with the clinicopathological features of patients with BC.
METHODS
Immunohistochemistry of CCL21 or CBS was performed in 18 intraductal cancer tissues, 124 invasive BC tissues, 50 paraneoplastic tissues, 50 lobular hyperplasia tissues, and 30 normal breast tissues. For cell experiments, two human BC cell lines (MDA-MB-231 and MCF-7) and a human breast epithelial cell line (MCF-10A) were utilized to detect the expression of CCL21 and CBS. After loss- and gain-of-function assays for CCL21 or CBS, the expression of CBS and CCL21 was measured by quantitative real-time polymerase chain reaction and western blot. Additionally, BC cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5-ethynyl-2'-deoxyuridine staining, and BC cell migration was determined by scratch test and Transwell assay.
RESULTS
In the clinical data, the positive rate of CCL21 or CBS was significantly higher in invasive BC tissues than in intraductal BC tissues, lobular hyperplasia tissues, paraneoplastic tissues, and normal breast tissues (p < 0.05 or p < 0.01). CBS or CCL21 expression shared close association with the clinicopathological characteristics and the poor prognosis of BC patients. In cell experiments, overexpression of CCL21 or CBS enhanced the proliferative and migratory abilities of BC cells.
CONCLUSION
CCL21 and CBS promoted BC cell migration and proliferation. CCL21 or CBS expression was strongly related to the poor prognosis of BC patients.
Topics: Humans; Female; Breast Neoplasms; Cystathionine beta-Synthase; Chemokines, CC; Hyperplasia; Ligands; Cell Proliferation; Cell Movement; Chemokine CCL21
PubMed: 35026764
DOI: 10.1159/000521671 -
Frontiers in Immunology 2023Immune responses highly depend on the effective trafficking of immune cells into and within secondary lymphoid organs (SLOs). Atypical chemokine receptors (ACKRs)...
Immune responses highly depend on the effective trafficking of immune cells into and within secondary lymphoid organs (SLOs). Atypical chemokine receptors (ACKRs) scavenge chemokines to eliminate them from the extracellular space, thereby generating gradients that guide leukocytes. In contrast to canonical chemokine receptors, ACKRs do not induce classical intracellular signaling that results in cell migration. Recently, the closest relative of ACKR3, GPR182, has been partially deorphanized as a potential novel ACKR. We confirm and extend previous studies by identifying further ligands that classify GPR182 as a broadly scavenging chemokine receptor. We validate the "atypical" nature of the receptor, wherein canonical G-protein-dependent intracellular signaling is not activated following ligand stimulation. However, β-arrestins are required for ligand-independent internalization and chemokine scavenging whereas the C-terminus is in part dispensable. In the absence of GPR182 , we observed elevated chemokine levels in the serum but also in SLO interstitium. We also reveal that CXCL13 and CCL28, which do not bind any other ACKR, are bound and efficiently scavenged by GPR182. Moreover, we found a cooperative relationship between GPR182 and ACKR3 in regulating serum CXCL12 levels, and between GPR182 and ACKR4 in controlling CCL20 levels. Furthermore, we unveil a new phenotype in GPR182-KO mice, in which we observed a reduced marginal zone (MZ), both in size and in cellularity, and thus in the T-independent antibody response. Taken together, we and others have unveiled a novel, broadly scavenging chemokine receptor, which we propose should be named ACKR5.
Topics: Animals; Mice; Chemokines, CC; Ligands; Signal Transduction; Receptors, Chemokine
PubMed: 37554323
DOI: 10.3389/fimmu.2023.1242531 -
BMC Urology Dec 2021Urothelial bladder cancer (BC) is one of the most prevalent malignancies with high mortality and high recurrence rate. Angiogenesis, tumor growth and metastasis of...
BACKGROUND
Urothelial bladder cancer (BC) is one of the most prevalent malignancies with high mortality and high recurrence rate. Angiogenesis, tumor growth and metastasis of multiple cancers are partly modulated by CC chemokines. However, we know little about the function of distinct CC chemokines in BC.
METHODS
ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER were used for analyzing differential expression, prognostic value, protein-protein interaction, genetic alteration and immune cell infiltration of CC chemokines in BC patients based on bioinformatics.
RESULTS
The results showed that transcriptional levels of CCL2/3/4/5/14/19/21/23 in BC patients were significantly reduced. A significant relation was observed between the expression of CCL2/11/14/18/19/21/23/24/26 and the pathological stage of BC patients. BC patients with high expression levels of CCL1, CCL2, CCL3, CCL4, CCL5, CCL8, CCL13, CCL15, CCL17, CCL18, CCL19, CCL22, CCL25, CCL27 were associated with a significantly better prognosis. Moreover, we found that differentially expressed CC chemokines are primarily correlated with cytokine activity, chemokines receptor binding, chemotaxis, immune cell migration. Further, there were significant correlations among the expression of CC chemokines and the infiltration of several types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells).
CONCLUSIONS
This study is an analysis to the potential role of CC chemokines in the therapeutic targets and prognostic biomarkers of BC, which gives a novel insight into the relationship between CC chemokines and BC.
Topics: Carcinoma, Transitional Cell; Chemokines, CC; Computational Biology; Humans; Prognosis; Tumor Cells, Cultured; Urinary Bladder Neoplasms
PubMed: 34893045
DOI: 10.1186/s12894-021-00938-w -
Mediators of Inflammation 2012Airway inflammation is accompanied by infiltration of inflammatory cells and an abnormal response of airway smooth muscle. These cells secrete chemokines and express the... (Review)
Review
Airway inflammation is accompanied by infiltration of inflammatory cells and an abnormal response of airway smooth muscle. These cells secrete chemokines and express the cell surface chemokine receptors that play an important role in the migration and degranulation of inflammatory cells. Omalizumab is a monoclonal antibody directed against immunoglobulin E, and its blocking of IgE signaling not only reduces inflammatory cell infiltration mediated by the Th2 immune response but also inhibits other immune responses. The chemokine CCL15 is influenced by omalizumab, and the source of CCL15 has been reported to be airway smooth muscle cells and basophils. CCL15 binds to its receptor CCR1, which has been reported to be expressed by various inflammatory cells and also by airway smooth muscle cells. Therefore, CCL15/CCR1 signaling could be a target for the treatment of asthma. We review the role of CCL15 in the pathogenesis of asthma and also discuss the influence of IgE-mediated immunomodulation via CCL15 and its receptor CCR1.
Topics: Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Asthma; Chemokines, CC; Clinical Trials as Topic; Humans; Immunoglobulin E; Interferon-gamma; Macrophage Inflammatory Proteins; Omalizumab; RNA, Messenger; Receptors, CCR1; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 23258953
DOI: 10.1155/2012/475253 -
European Journal of Immunology Jan 1998Two subpopulations of human T lymphocytes expressing different antigen receptors, alpha/beta and gamma/delta, emigrate into inflamed tissues in distinctive patterns. We... (Comparative Study)
Comparative Study
Two subpopulations of human T lymphocytes expressing different antigen receptors, alpha/beta and gamma/delta, emigrate into inflamed tissues in distinctive patterns. We compared the transmigration of alpha/beta and gamma/delta T cells to C-C and C-X-C chemokines using an in vitro transendothelial chemotaxis assay. The C-C chemokines monocyte chemoattractant protein (MCP)-1, RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta stimulated similar, dose-dependent chemotaxis of purified gamma/delta T cells, whereas MCP-1, RANTES, and MIP-1alpha produced greater chemotaxis of purified alpha/beta T cells than MIP-1beta. In contrast, the C-X-C chemokines interleukin (IL)-8 and interferon-gamma inducible protein-10 (IP-10) did not promote chemotaxis of either alpha/beta or gamma/delta T cells. Three gamma/delta T cell clones with differing CD4 and CD8 phenotypes also migrated exclusively to C-C chemokines. Phenotypic analysis of mononuclear cells that transmigrated from an input population of unfractionated peripheral blood mononuclear cells confirmed the results with purified gamma/delta T cells. Our data demonstrate that human peripheral blood alpha/beta and gamma/delta T cells can transmigrate to MCP-1, RANTES, MIP-1alpha, and MIP-1beta, and suggest that both T lymphocyte subpopulations share the capacity to emigrate in response to C-C chemokines during inflammation.
Topics: Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5; Chemokine CXCL10; Chemokines; Chemokines, CXC; Chemotactic Factors; Chemotaxis, Leukocyte; Dose-Response Relationship, Immunologic; Endothelium, Vascular; Humans; Inflammation; Macrophage Inflammatory Proteins; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Antigen, T-Cell, gamma-delta; Recombinant Proteins; T-Lymphocyte Subsets
PubMed: 9485190
DOI: 10.1002/(SICI)1521-4141(199801)28:01<104::AID-IMMU104>3.0.CO;2-F