scholarly journals Patient-Oriented Perspective on Chemokine Receptor Expression and Function in Glioma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 130
Author(s):  
Damla Isci ◽  
Giulia D’Uonnolo ◽  
May Wantz ◽  
Bernard Rogister ◽  
Arnaud Lombard ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Data ◽  
Expression Profile ◽  
Chemokine Receptor ◽  
Brain Region ◽  
Chemokine Receptors ◽  
Receptor Expression ◽  
Cell Type ◽  
Specific Receptor ◽  
And Function

Gliomas are severe brain malignancies, with glioblastoma (GBM) being the most aggressive one. Despite continuous efforts for improvement of existing therapies, overall survival remains poor. Over the last years, the implication of chemokines and their receptors in GBM development and progression has become more evident. Recently, large amounts of clinical data have been made available, prompting us to investigate chemokine receptors in GBM from a still-unexplored patient-oriented perspective. This study aims to highlight and discuss the involvement of chemokine receptors—CCR1, CCR5, CCR6, CCR10, CX3CR1, CXCR2, CXCR4, ACKR1, ACKR2, and ACKR3—most abundantly expressed in glioma patients based on the analysis of publicly available clinical datasets. Given the strong intratumoral heterogeneity characterizing gliomas and especially GBM, receptor expression was investigated by glioma molecular groups, by brain region distribution, emphasizing tissue-specific receptor functions, and by cell type enrichment. Our study constitutes a clinically relevant and patient-oriented guide that recapitulates the expression profile and the complex roles of chemokine receptors within the highly diversified glioma landscape. Additionally, it strengthens the importance of patient-derived material for development and precise amelioration of chemokine receptor-targeting therapies.

Chemokine Receptor Expression Profile in the Model of Parotid MALT Lymphomagenesis: De Novo Expression of CXCR6.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2622-2622
Author(s):  
Alexander J.A. Deutsch ◽  
Ariane Aigelsreiter ◽  
Elisabeth Steinbauer ◽  
Werner Linkesch ◽  
Christine Beham-Schmid ◽  
...  
Keyword(s):  
Expression Profile ◽  
Malt Lymphoma ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
De Novo ◽  
B Cell Lymphoma ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Parotid Glands ◽  
Chemokine Receptor Expression

Abstract Chemokine receptors mediate migration and activation of lymphocytes through binding of their ligands. Several recent studies have revealed important contributions of chemokine receptors and their ligands to the development and progression/dissemination of hematopoietic neoplasms. Strong expression of CXCR5 and its ligand BCA-1 was detected in transformed B cells in H. pylori positive gastric MALT lymphoma. Because the knowledge of chemokine receptor expression in parotid MALT lymphoma is limited, we performed a comprehensive study on tissue samples of parotid glands (P), parotid glands affected by Sjoegren Syndrome (SS), parotid MALT lymphoma (MALT) and extranodal diffuse large B cell lymphoma (eDLBCL). By investigating the expression of all 19 known chemokine receptor at mRNA levels by real time PCR using a semi quantitative approach and of 3 chemokine receptors (CCR1, CCR5 and CXCR6) at protein levels we propose a model of MALT lymphoma that the development from a non neoplastic event to Sjoegren Syndrome or malignant transformation is accompanied by significant deregulations in the chemokine receptor expression profile: in the development of SS CCR5 was 783 times up regulated and CCR6, CCR8 and CCR10 mRNAs were de novo expressed; in the progression process of SS to parotid MALT CCR7, CXCR3, CXCR4, CXCR5, CXCR6, CX3CR1 and XCR1 were de novo expressed and CCR10 lost its expression; during the transformation of MALT to eDLBCL, CCR1, CCR8 and CXCR3 were 13 times down regulated and CX3CR1 and XCR1 lost their expression. Expression of CCR1, CCR5 and CXCR6 were confirmed by immunohistochemistry. The present results support a model of a stepwise progression of parotid MALT lymphoma from a non neoplastic event to Sjoegren Syndrome and finally overt MALT lymphoma guided by differentially expressed chemokine receptors and their ligands.

scholarly journals Differential Regulation of Gonadotropins as Revealed by Transcriptomes of Distinct LH and FSH Cells of Fish Pituitary

2021 ◽  
Vol 22 (12) ◽  
pp. 6478
Author(s):  
Lian Hollander-Cohen ◽  
Matan Golan ◽  
Berta Levavi-Sivan
Keyword(s):  
Follicle Stimulating Hormone ◽  
Differential Regulation ◽  
Receptor Expression ◽  
Hormone Regulation ◽  
Fish Reproduction ◽  
Cell Type ◽  
Conserved Genes ◽  
Transgenic Tilapia ◽  
And Function ◽  
Direct Regulation

From mammals to fish, reproduction is driven by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) temporally secreted from the pituitary gland. Teleost fish are an excellent model for addressing the unique regulation and function of each gonadotropin cell since, unlike mammals, they synthesize and secrete LH and FSH from distinct cells. Only very distant vertebrate classes (such as fish and birds) demonstrate the mono-hormonal strategy, suggesting a potential convergent evolution. Cell-specific transcriptome analysis of double-labeled transgenic tilapia expressing GFP and RFP in LH or FSH cells, respectively, yielded genes specifically enriched in each cell type, revealing differences in hormone regulation, receptor expression, cell signaling, and electrical properties. Each cell type expresses a unique GPCR signature that reveals the direct regulation of metabolic and homeostatic hormones. Comparing these novel transcriptomes to that of rat gonadotrophs revealed conserved genes that might specifically contribute to each gonadotropin activity in mammals, suggesting conserved mechanisms controlling the differential regulation of gonadotropins in vertebrates.

scholarly journals Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 8
Author(s):  
Paulina Lewandowska ◽  
Jaroslaw Wierzbicki ◽  
Marek Zawadzki ◽  
Anil Agrawal ◽  
Małgorzata Krzystek-Korpacka
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Chemokine Receptor ◽  
Growth Pattern ◽  
Chemokine Receptors ◽  
Receptor Expression ◽  
Transcriptional Analysis ◽  
Neoplastic Tissue ◽  
Node Metastasis ◽  
Affected Tissue

Facilitating resolution of inflammation using atypical chemokine receptors (ACKR) as an anticancer strategy is considered but requires a deeper understanding of receptor role in carcinogenesis. We aimed at transcriptional analysis (RTqPCR) of ACKR2 and ACKR4 expression in colorectal adenoma-adenocarcinoma sequence in paired normal-neoplastic tissues from 96 polyps and 51 cancers. On average, ACKR2 was downregulated in neoplastic as compared to non-affected tissue in polyp (by 2.7-fold) and cancer (by 3.1-fold) patients. The maximal downregulation (by 8.2-fold) was observed in adenomas with the highest potential for malignancy and was gradually lessening through cancer stages I-IV, owing to increased receptor expression in tumors. On average, ACKR4 was significantly downregulated solely in adenocarcinomas (by 1.5-fold), less so in patients with lymph node metastasis, owing to a gradual decrease in ACKR4 expression among N0-N1-N2 cancers in non-affected tissue without changes in tumors. In adenomas, ACKR4 downregulation in neoplastic tissue increased with increasing potential for malignancy and contribution of villous growth pattern. ACKR4 expression increased in non-affected tissue with a concomitant decrease in pathological mucosa. In conclusion, the changes in ACKRs expression occur already in precancerous colorectal lesions, culminating in the adenomas with the highest potential for malignancy. Therefore, chemoprevention by manipulating ACKRs’ expression is worth exploration.

scholarly journals Airway smooth muscle chemokine receptor expression and function in asthma

2009 ◽  
Vol 39 (11) ◽  
pp. 1684-1692 ◽  
Author(s):  
R. Saunders ◽  
A. Sutcliffe ◽  
D. Kaur ◽  
S. Siddiqui ◽  
F. Hollins ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Chemokine Receptor ◽  
Receptor Expression ◽  
Chemokine Receptor Expression ◽  
And Function

Chemokine receptor expression profile of eosinophils in disordered conditions

2002 ◽  
Vol 109 (1) ◽  
pp. S165-S165
Author(s):  
Hiroyuki Nagase ◽  
Koichiro Kudo ◽  
Shinyu Izumi ◽  
Ken Ohta ◽  
Nobuyuki Kobayashi ◽  
...  
Keyword(s):  
Expression Profile ◽  
Chemokine Receptor ◽  
Receptor Expression ◽  
Chemokine Receptor Expression

scholarly journals Chemokine and Chemokine Receptor Dynamics during Genital Chlamydial Infection

2002 ◽  
Vol 70 (2) ◽  
pp. 844-850 ◽  
Author(s):  
Tesfaye Belay ◽  
Francis O. Eko ◽  
Godwin A. Ananaba ◽  
Samera Bowers ◽  
Terri Moore ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Primary Infection ◽  
Chlamydial Infection ◽  
Time Course ◽  
Secondary Infection ◽  
Receptor Expression ◽  
Microbial Pathogens ◽  
Intercellular Adhesion Molecule ◽  
Regulation Of Expression

ABSTRACT Current design strategies for vaccines against certain microbial pathogens, including Chlamydia trachomatis, require the induction and targeting of specific immune effectors to the local sites of infection known as the mucosal effector sites. Chemokines and their receptors are important mediators of leukocyte trafficking and of the controlled recruitment of specific leukocyte clonotypes during host defense against infections and during inflammation. We analyzed the dynamics of chemokine and chemokine receptor expression in genital mucosae during genital chlamydial infection in a murine model to determine how these molecular entities influence the development of immunity and the clearance of infection. A time course study revealed an increase of up to threefold in the levels of expression of RANTES, monocyte chemotactic protein 1 (MCP-1), gamma-interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1α (MIP-1α), and intercellular adhesion molecule type 1 (ICAM-1) after genital infection with the C. trachomatis agent of mouse pneumonitis. Peak levels of expression of RANTES, MCP-1, and MIP-1α occurred by day 7 after primary infection, while those of IP-10 and ICAM-1 peaked by day 21. Expression levels of these molecules decreased by day 42 after primary infection, by which time all animals had resolved the infection, suggesting an infection-driven regulation of expression. A rapid upregulation of expression of these molecules was observed after secondary infection. The presence of cells bearing the chemokine receptors CCR5 and CXCR3, known to be preferentially expressed on Th1 and dendritic cells, was also synchronous with the kinetics of immune induction in the genital tract and clearance of infection. Results demonstrated that genital chlamydial infection is associated with a significant induction of chemokines and chemokine receptors that are involved in the recruitment of Th1 cells into the site of infection. Future studies will focus on how selective modulation of chemokines and their receptors can be used to optimize long-term immunity against Chlamydia.

Neuropeptide substance P upregulates chemokine and chemokine receptor expression in primary mouse neutrophils

2007 ◽  
Vol 293 (2) ◽  
pp. C696-C704 ◽  
Author(s):  
Jia Sun ◽  
Raina Devi Ramnath ◽  
Madhav Bhatia
Keyword(s):  
Substance P ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Binding Activity ◽  
Receptor Expression ◽  
Chemokine Production ◽  
Chemokine Receptor Expression ◽  
Cc Chemokine ◽  
Primary Mouse ◽  
Cxc Chemokine

Neuropeptides play an important role in the active communication between the nervous and immune systems. Substance P (SP) is a prominent neuropeptide involved in neurogenic inflammation and has been reported to exert various proinflammatory actions on inflammatory leukocytes including neutrophils. The present study further investigated the modulatory effect of SP (1 μM) on chemokine production and chemokine receptor expression in primary mouse neutrophils. Our results showed that SP primed neutrophils for chemotactic responses not only to the CXC chemokine macrophage inflammatory protein (MIP)-2/CXCL2 but also to the CC chemokine MIP-1α/CCL3. The activating effect of SP on neutrophils was further evidenced by upregulation of the CD11b integrin, the activation marker of neutrophils. SP induced both the mRNA and protein expression of the chemokines MIP-1α/CCL3 and MIP-2/CXCL2 in neutrophils and upregulated the chemokine receptors CC chemokine receptor (CCR)-1 and CXC chemokine receptor (CXCR)-2. This stimulatory effect on chemokine and chemokine receptor expression in neutrophils was further found to be neurokinin-1 receptor (NK-1R) specific. Pretreatment with selective NK-1R antagonists inhibited SP-triggered activation of neutrophils and chemokine and chemokine receptor upregulation. Moreover, SP-induced chemokine upregulation was NF-κB dependent. SP time dependently induced NF-κB p65 binding activity, IκBα degradation, and NF-κB p65 nuclear translocation in neutrophils. Inhibition of NF-κB activation with its inhibitor Bay11-7082 (10 μM) abolished SP-induced NF-κB binding activity and upregulation of MIP-1α/CCL3 and MIP-2/CXCL2 in neutrophils. Together, these results suggest that SP exerts a direct stimulatory effect on the expression of chemokines and chemokine receptors in mouse neutrophils. The effect is NK-1R mediated, involving NF-κB activation.

Soluble HLA-G dampens CD94/NKG2A expression and function and differentially modulates chemotaxis and cytokine and chemokine secretion in CD56bright and CD56dim NK cells

Blood ◽  
2011 ◽  
Vol 118 (22) ◽  
pp. 5840-5850 ◽  
Author(s):  
Fabio Morandi ◽  
Elisa Ferretti ◽  
Roberta Castriconi ◽  
Alessandra Dondero ◽  
Andrea Petretto ◽  
...  
Keyword(s):  
Nk Cells ◽  
Chemokine Receptor ◽  
Nk Cell ◽  
Receptor Expression ◽  
Regulated Secretion ◽  
Cell Functions ◽  
Soluble Hla ◽  
Ifn Γ ◽  
And Function ◽  
Nk Receptor

Abstract Soluble HLA-G (sHLA-G) inhibits natural killer (NK) cell functions. Here, we investigated sHLA-G–mediated modulation of (1) chemokine receptor and NK receptor expression and function and (2) cytokine and chemokine secretion in CD56bright and CD56dim NK cells. sHLA-G-treated or untreated peripheral blood (PB) and tonsil NK cells were analyzed for chemokine receptor and NK receptor expression by flow cytometry. sHLA-G down-modulated (1) CXCR3 on PB and tonsil CD56bright and CD56dim, (2) CCR2 on PB and tonsil CD56bright, (3) CX3CR1 on PB CD56dim, (4) CXCR5 on tonsil CD56dim, and (5) CD94/NKG2A on PB and tonsil CD56bright and CD56dim NK cells. Such sHLA-G–mediated down-modulations were reverted by adding anti–HLA-G or anti–ILT2 mAbs. sHLA-G inhibited chemotaxis of (1) PB NK cells toward CXCL10, CXCL11, and CX3CL1 and (2) PB CD56bright NK cells toward CCL2 and CXCL10. IFN-γ secretion induced by NKp46 engagement was inhibited by NKG2A engagement in untreated but not in sHLA-G–treated NK cells. sHLA-G up-regulated secretion of (1) CCL22 in CD56bright and CD56dim and (2) CCL2, CCL8, and CXCL2-CXCL3 in CD56dim PB NK cells. Signal transduction experiments showed sHLA-G–mediated down-modulation of Stat5 phosphorylation in PB NK cells. In conclusion, our data delineated novel mechanisms of sHLA-G–mediated inhibition of NK-cell functions.

scholarly journals E-protein–regulated expression of CXCR4 adheres preselection thymocytes to the thymic cortex

2019 ◽  
Vol 216 (8) ◽  
pp. 1749-1761 ◽  
Author(s):  
Tejas Kadakia ◽  
Xuguang Tai ◽  
Michael Kruhlak ◽  
Jan Wisniewski ◽  
Il-Young Hwang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Cxcr4 Expression ◽  
Receptor Expression ◽  
Thymic Epithelial Cells ◽  
E Protein ◽  
Regulated Expression ◽  
Genes Encoding ◽  
Protein Transcription

Preselection thymocytes are normally retained in the thymic cortex, but the mechanisms responsible remain incompletely understood. We now report that deletion of genes encoding the E-protein transcription factors E2A and HEB disorders chemokine receptor expression on developing thymocytes to allow escape of preselection TCR−CD8+ thymocytes into the periphery. We document that CXCR4 expression normally anchors preselection thymocytes to the thymic cortex via interaction with its ligand CXCL12 on cortical thymic epithelial cells, and that disruption of CXCR4–CXCL12 engagements release preselection thymocytes from the thymic cortex. We further document that CXCR4 expression must be extinguished by TCR-mediated positive selection signals to allow migration of TCR-signaled thymocytes out of the thymic cortex into the medulla. Thus, E-protein transcription factors regulate the ordered expression pattern of chemokine receptors on developing thymocytes, and the interaction of the chemokine receptor CXCR4 with its ligand adheres TCR-unsignaled preselection thymocytes to the thymic cortex.

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