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The Role and Mechanism of P2X7 Receptor in Cancer and Inflammatory Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 30 July 2024 | Viewed by 1038

Special Issue Editor


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Guest Editor
Department of Medical Sciences, University of Ferrara, Via Borsari 46, 44121 Ferrara, Italy
Interests: cancer research; cell culture; immunology; molecular biology; cancer biology; signaling pathways; cell biology; antibodies; inflammation; flow cytometry

Special Issue Information

Dear Colleagues,

The purpose of this Special Issue is to summarize the roles and mechanisms of P2X7 receptors in human diseases, particularly in cancer and inflammatory diseases. The P2X7 receptor is an ATP-gated non-selective cation channel that is widely expressed in a variety of immune and nonimmune cells. P2X7 receptors play a key role in inflammation and immunomodulation, such as signal transduction and the activation of immune cells. The activity of P2X7 receptors in tumour growth and dissemination is also of interest. The awareness about the role of P2X7 in human diseases and the consideration of the P2X7 receptor as a potential target for the treatment of inflammatory diseases and cancer are constantly increasing.

This Special Issue aims to publish high-quality manuscripts that provide insights into the molecular mechanisms of P2X7 receptors in cancer and inflammatory diseases.

Dr. Anna Lisa Giuliani
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • P2X7 receptor
  • inflammation
  • cancer
  • purinergic signalling

Published Papers (2 papers)

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Research

12 pages, 295 KiB  
Article
Genetic Polymorphisms of P2RX7 but Not of ADORA2A Are Associated with the Severity of SARS-CoV-2 Infection
by Jorge Lindo, Célia Nogueira, Rui Soares, Nuno Cunha, Maria Rosário Almeida, Lisa Rodrigues, Patrícia Coelho, Francisco Rodrigues, Rodrigo A. Cunha and Teresa Gonçalves
Int. J. Mol. Sci. 2024, 25(11), 6135; https://doi.org/10.3390/ijms25116135 - 2 Jun 2024
Abstract
SARS-CoV-2 infection ranges from mild to severe presentations, according to the intensity of the aberrant inflammatory response. Purinergic receptors dually control the inflammatory response: while adenosine A2A receptors (A2ARs) are anti-inflammatory, ATP P2X7 receptors (P2X7Rs) exert pro-inflammatory effects. The aim of this study [...] Read more.
SARS-CoV-2 infection ranges from mild to severe presentations, according to the intensity of the aberrant inflammatory response. Purinergic receptors dually control the inflammatory response: while adenosine A2A receptors (A2ARs) are anti-inflammatory, ATP P2X7 receptors (P2X7Rs) exert pro-inflammatory effects. The aim of this study was to assess if there were differences in allelic and genotypic frequencies of a loss-of-function SNP of ADORA2A (rs2298383) and a gain-of-function single nucleotide polymorphism (SNP) of P2RX7 (rs208294) in the severity of SARS-CoV-2-associated infection. Fifty-five individuals were enrolled and categorized according to the severity of the infection. Endpoint genotyping was performed in blood cells to screen for both SNPs. The TT genotype (vs. CT + CC) and the T allele (vs. C allele) of P2RX7 SNP were found to be associated with more severe forms of COVID-19, whereas the association between ADORA2A SNP and the severity of infection was not significantly different. The T allele of P2RX7 SNP was more frequent in people with more than one comorbidity and with cardiovascular conditions and was associated with colorectal cancer. Our findings suggest a more prominent role of P2X7R rather than of A2AR polymorphisms in SARS-CoV-2 infection, although larger population-based studies should be performed to validate our conclusions. Full article
17 pages, 2828 KiB  
Article
Post-Transplant Cyclophosphamide Combined with Brilliant Blue G Reduces Graft-versus-Host Disease without Compromising Graft-versus-Leukaemia Immunity in Humanised Mice
by Peter Cuthbertson, Amy Button, Chloe Sligar, Amal Elhage, Kara L. Vine, Debbie Watson and Ronald Sluyter
Int. J. Mol. Sci. 2024, 25(3), 1775; https://doi.org/10.3390/ijms25031775 - 1 Feb 2024
Viewed by 875
Abstract
Allogeneic haematopoietic stem cell transplantation (HSCT) leads to the establishment of graft-versus-leukaemia (GVL) immunity, but in many cases also results in the development of graft-versus-host disease (GVHD). This study aimed to determine if P2X7 antagonism using Brilliant Blue G (BBG) could improve the [...] Read more.
Allogeneic haematopoietic stem cell transplantation (HSCT) leads to the establishment of graft-versus-leukaemia (GVL) immunity, but in many cases also results in the development of graft-versus-host disease (GVHD). This study aimed to determine if P2X7 antagonism using Brilliant Blue G (BBG) could improve the beneficial effects of post-transplant cyclophosphamide (PTCy) in a humanised mouse model of GVHD, without comprising GVL immunity. NOD.Cg-Prkdcscid Il2rgtm1Wjl (NSG) mice were injected with human peripheral blood mononuclear cells (PBMCs) (Day 0), then with cyclophosphamide (33 mg/kg) on Days 3 and 4, and with BBG (50 mg/kg) (or saline) on Days 0–10. PTCy with BBG reduced clinical GVHD development like that of PTCy alone. However, histological analysis revealed that the combined treatment reduced liver GVHD to a greater extent than PTCy alone. Flow cytometric analyses revealed that this reduction in liver GVHD by PTCy with BBG corresponded to an increase in human splenic CD39+ Tregs and a decrease in human serum interferon-γ concentrations. In additional experiments, humanised NSG mice, following combined treatment, were injected with human THP-1 acute myeloid leukaemia cells on Day 14. Flow cytometric analyses of liver CD33+ THP-1 cells showed that PTCy with BBG did not mitigate GVL immunity. In summary, PTCy combined with BBG can reduce GVHD without compromising GVL immunity. Future studies investigating P2X7 antagonism in combination with PTCy may lead to the development of novel treatments that more effectively reduce GVHD in allogeneic HSCT patients without promoting leukaemia relapse. Full article
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