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Atypical chemokine receptor d6

Reyes Niradiz, Benedetti Ines, Rebollo Juan, Correa Oscar, Geliebter Jan
Atypical chemokine receptors have recently emerged as important molecular players in health and diseases; they affect chemokine availability and function and impact a multitude of pathophysiological events, including the tumorigenesis process. This family of atypical receptors comprises five members: ACKR1/DARC, ACKR2/D6, ACKR3/CXCR7, ACKR4/CCRL1, and ACKR5/CCRL2. This work evaluated the differential expression of these receptors in prostate cancer using quantitative PCR. Further evaluation of CCRL2 at the protein level confirmed its overexpression in a metastatic cell line and in malignant prostatic tissues from patients...
November 1, 2017: Journal of Biomedical Research
Andrei Bideak, Alexander Blaut, John M Hoppe, Martin B Müller, Giuseppina Federico, Nuru Eltrich, Hermann-Josef Gröne, Massimo Locati, Volker Vielhauer
The atypical chemokine receptor 2 (ACKR2), also named D6, regulates local levels of inflammatory chemokines by internalization and degradation. To explore potential anti-inflammatory functions of ACKR2 in glomerulonephritis, we induced autologous nephrotoxic nephritis in C57/BL6 wild-type and Ackr2-deficient mice. Renal ACKR2 expression increased and localized to interstitial lymphatic endothelium during nephritis. At two weeks Ackr2-/- mice developed increased albuminuria and urea levels compared to wild-type mice...
April 2018: Kidney International
Miran Aswad, Simaan Assi, Sagie Schif-Zuck, Amiram Ariel
The engulfment of apoptotic polymorphonuclear cells (PMN) during the resolution of inflammation leads to macrophage reprogramming culminating in reduced proinflammatory and increased anti-inflammatory mediator secretion. The atypical chemokine receptor D6/ACKR2 is expressed on apoptotic PMN and plays an important role in regulating macrophage properties during and after engulfment. In this study, we found that the inflammatory chemokine CCL5 is mostly retained (75%) during the resolution of zymosan A peritonitis in mice...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Valentina Salvi, Francesca Sozio, Silvano Sozzani, Annalisa Del Prete
Inflammatory reactions occurring in the central nervous system (CNS), known as neuroinflammation, are key components of the pathogenic mechanisms underlying several neurological diseases. The chemokine system plays a crucial role in the recruitment and activation of immune and non-immune cells in the brain, as well as in the regulation of microglia phenotype and function. Chemokines belong to a heterogeneous family of chemotactic agonists that signal through the interaction with G protein-coupled receptors (GPCRs)...
2017: Frontiers in Aging Neuroscience
Matteo Massara, Ornella Bonavita, Alberto Mantovani, Massimo Locati, Raffaella Bonecchi
The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity...
June 2016: Journal of Leukocyte Biology
Pek Joo Teoh, Fiona M Menzies, Chris A H Hansell, Mairi Clarke, Carolann Waddell, Graham J Burton, Scott M Nelson, Robert J B Nibbs
Inflammatory chemokines produced in the placenta can direct the migration of placental leukocytes using chemokine receptors that decorate the surface of these cells. Fetal trophoblasts can also express receptors for inflammatory chemokines, and they are one of the few cell types that express atypical chemokine receptor 2 (ACKR2), previously known as D6. ACKR2 binds many inflammatory CC chemokines but cannot stimulate cell migration or activate signaling pathways used by conventional chemokine receptors. Existing evidence suggests that ACKR2 is a specialized chemokine scavenger, but its function in primary human trophoblasts has not been explored...
November 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Valgerdur Tomasdottir, Arnor Vikingsson, Ingibjorg Hardardottir, Jona Freysdottir
Murine zymosan-induced peritonitis is the model most frequently used to study resolution of inflammation. However, the antigen-induced peritonitis model may be better suited for studying resolution of inflammation and the adaptive phase that follows. The objective of this study was to provide an evaluation of the kinetics of cells and mediators during induction, resolution and the adaptive immune phases of a murine antigen-induced inflammation. Female C57BL/6 mice were immunized twice subcutaneously with mBSA and three weeks after the initial immunization they were injected intraperitoneally (i...
December 15, 2014: Journal of Immunological Methods
Xiao-Hua Zeng, Zhou-Luo Ou, Ke-Da Yu, Lan-Yun Feng, Wen-Jing Yin, Jing Li, Zhen-Zhou Shen, Zhi-Min Shao
The aim of this study was to determine the frequency of axillary lymph node (ALN) metastasis of early breast cancers by evaluating the status of DARC, D6 and CCX-CKR and the levels of VEGF and MMP-9. The status of DARC, D6 and CCX-CKR and the levels VEGF and MMP-9 were evaluated in ALN- (n = 130) and ALN + (n = 88) patients with T1 breast cancer by immunohistochemical staining. For ALN, likelihood ratio χ (2)-tests were used for univariate analysis and logistic regression for multivariate analysis. Univariate analysis identified the nuclear grade, VEGF and MMP-9 expression and absence of DARC, D6 and CCX-CKR as predictors of ALN involvement...
September 2014: Medical Oncology
Benedetta Savino, Nicoletta Caronni, Achille Anselmo, Fabio Pasqualini, Elena Monica Borroni, Gianluca Basso, Giuseppe Celesti, Luigi Laghi, Athanasia Tourlaki, Vinicio Boneschi, Lucia Brambilla, Manuela Nebuloni, Gianluca Vago, Alberto Mantovani, Massimo Locati, Raffaella Bonecchi
D6 is an atypical chemokine receptor acting as a decoy and scavenger for inflammatory CC chemokines expressed in lymphatic endothelial cells. Here, we report that D6 is expressed in Kaposi sarcoma (KS), a tumor ontogenetically related to the lymphatic endothelium. Both in human tumors and in an experimental model, D6 expression levels were inversely correlated with tumor aggressiveness and increased infiltration of proangiogenic macrophages. Inhibition of monocyte recruitment reduced the growth of tumors, while adoptive transfer of wild-type, but not CCR2(-/-) macrophages, increased the growth rate of D6-competent neoplasms...
July 2014: Cancer Immunology Research
Ai Lan Chew, Wee Yee Tan, Boon Yin Khoo
Apart from their major function in the coordination of leukocyte recruitment, chemokines, in cooperation with their receptors, have been implicated in the progression of various diseases including different types of cancer, affecting survival, proliferation and metastasis. A complex network of chemokines and receptors exists in the tumor microenvironment and affects tumor development in various ways where chemokines activate typical signalling pathways by binding to the respective receptors. The identification and characterization of a group of atypical chemokine receptors [D6, Duffy antigen receptor for chemokines (DARC), ChemoCentryx chemokine receptor (CCX-CKR) and CXCR7] which appear to use unique biochemical properties to regulate the biological activities of these chemokines, is useful in the effort to therapeutically manipulate chemokines in a broad spectrum of diseases in which these chemokines play a critical role...
March 2013: Biomedical Reports
Feng Ying Wu, Jiang Fan, Liang Tang, Yin Min Zhao, Cai Cun Zhou
Chemokines and their receptors have been shown to play a vital role in lung cancer progression. D6 is an atypical chemokine receptor which is able to internalize and degrade chemokines. To investigate the potential role of D6 in lung cancer, we established D6-overexpressing A549 lung cancer cell lines by the transfection of human D6 cDNA. Results showed that D6 inhibited the proliferation of cancer cells in vitro and tumorigenesis in vivo. We also determined chemokine levels in the supernatant and showed that a number of chemokines (CCL2/4/5) had significantly decreased protein levels in D6-overexpressing cells compared with the controls, whereas no significant changes in mRNA expression levels of these chemokines were detected...
July 2013: Oncology Letters
Antal Rot, Clive McKimmie, Claire L Burt, Kenneth J Pallas, Thomas Jamieson, Monika Pruenster, Richard Horuk, Robert J B Nibbs, Gerard J Graham
Chemokines, acting on their cognate receptors on infiltrating leukocytes, drive the inflammatory response. We have been interested in determining roles and potential mechanisms for the atypical chemokine-scavenging receptor D6 in the regulation of inflammation. In this study, we show that a psoriasis-like pathology that arises in inflamed skins of D6-deficient mice is characterized by a massive and aberrant localization of neutrophils to the dermal/epidermal junction, which is associated with development of the pathology...
June 15, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
Elena M Borroni, Cinzia Cancellieri, Alessandro Vacchini, Yann Benureau, Bernard Lagane, Françoise Bachelerie, Fernando Arenzana-Seisdedos, Kensaku Mizuno, Alberto Mantovani, Raffaella Bonecchi, Massimo Locati
Chemokines promote the recruitment of leukocytes to sites of infection and inflammation by activating conventional heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). Chemokines are also recognized by a set of atypical chemokine receptors (ACRs), which cannot induce directional cell migration but are required for the generation of chemokine gradients in tissues. ACRs are presently considered "silent receptors" because no G protein-dependent signaling activity is observed after their engagement by cognate ligands...
April 30, 2013: Science Signaling
Teng Hou, Dongxia Liang, Liqun Xu, Xin Huang, Yongwen Huang, Yanna Zhang
OBJECTIVE: Atypical chemokine receptors (ACRs), including CCX-CKR, DARC, and D6, have been reported to be involved in cancer invasion and metastasis. The objective of this study was to investigate the prognostic importance of ACRs in patients with cervical squamous cell carcinoma (CSCC). METHODS: The expression of three ACRs was investigated by immunohistochemical (IHC) examination in a total of 317 cervical specimens including 40 normal cervical tissues, 50 cases of carcinoma in situ of cervix (CIS), and 227 cases of CSCC by immunohistochemistry...
July 2013: Gynecologic Oncology
Zhi Zhu, Zhe Sun, Zhenning Wang, Pengtao Guo, Xinyu Zheng, Huimian Xu
BACKGROUND: Atypical chemokine receptors (ACRs), which serve as a decoy receptor to attract chemokines, including DARC, D6, and CCX-CKR, have an important role in inhibiting invasion and metastasis of cancer cells; however, their expression in gastric cancer has not been characterized. The purpose of this study was to determine the predictive value of ACRs for overall survival in gastric cancer. METHODS: We performed immunohistochemical analysis on formalin-fixed, paraffin-embedded cancer tissue and used Western blot analysis on cell lines with an antibody against ACR protein...
July 2013: Journal of Surgical Research
Elena Borroni, Cinzia Cancellieri, Massimo Locati, Raffaella Bonecchi
Atypical chemokine receptors are a distinct subset of chemokine receptors able to modulate immune responses by acting as chemokine decoy/scavengers or transporters. Intracellular trafficking properties sustained by Gαi-independent signaling have emerged as a major determinant of their biological properties, which support continuous uptake, transport, and/or concentration, of the ligands. Here, we are providing methods to study both trafficking and signaling of this class of chemokine receptors focusing on the atypical chemokine receptor D6 that degrades inflammatory CC chemokines...
2013: Methods in Enzymology
Gerard J Graham, Massimo Locati
Chemokines and their receptors are key regulators of leukocyte migration and intra-tissue accumulation under both homeostatic and inflammatory conditions. Regulation of chemokine-dependent responses, particularly those relating to inflammation, is essential to avoid the development of inflammatory and autoimmune pathologies. Recently, a new subfamily of chemokine receptors referred to as the 'atypical' chemokine receptors has emerged, members of which have been shown to play important roles in controlling in vivo chemokine biology...
January 2013: Journal of Pathology
Cinzia Cancellieri, Nicoletta Caronni, Alessandro Vacchini, Benedetta Savino, Elena M Borroni, Massimo Locati, Raffaella Bonecchi
The atypical chemokine receptor D6 was initially called "silent" on the basis of lack of conventional signaling events that lead to directional cell migration. It has emerged that D6 is able to bind and drive to degradative compartments most inflammatory CC chemokines and that is able to convey G-protein independent signaling events to optimize its scavenging activity. We here summarize the knowledge available today on D6 structural and signaling properties and its essential role for the control of inflammatory cells traffic and proper development of the adaptive immune response...
August 2013: Molecular Immunology
Erica Bazzan, Marina Saetta, Graziella Turato, Elena M Borroni, Cinzia Cancellieri, Simonetta Baraldo, Benedetta Savino, Fiorella Calabrese, Andrea Ballarin, Elisabetta Balestro, Alberto Mantovani, Manuel G Cosio, Raffaella Bonecchi, Massimo Locati
BACKGROUND: D6 is an atypical chemokine receptor involved in chemokine degradation and resolution of acute inflammatory responses in mice. Emerging evidence suggests that D6 might behave differently in human chronic inflammatory conditions. We, therefore, investigated the involvement of D6 in the immune responses in COPD, a chronic inflammatory condition of the lung. METHODS: D6 expression was quantified by immunohistochemistry in surgical resected lung specimens from 16 patients with COPD (FEV(1), 57% ± 6% predicted) and 18 control subjects with normal lung function (nine smokers and nine nonsmokers)...
January 2013: Chest
G J Graham, M Locati, A Mantovani, A Rot, M Thelen
A subset of chemokine receptors, initially called "silent" on the basis of their apparent failure to activate conventional signalling events, has recently attracted growing interest due to their ability to internalize, degrade, or transport ligands and thus modify gradients and create functional chemokine patterns in tissues. These receptors recognize distinct and complementary sets of ligands with high affinity, are strategically expressed in different cellular contexts, and lack structural determinants supporting Gα(i) activation, a key signalling event in cell migration...
July 30, 2012: Immunology Letters
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