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The P2X7 Receptor in Infection and Inflammation
Open accessAbstract
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known. The P2X7R is a potent stimulant of inflammation and immunity and a promoter of cancer cell growth. This makes P2X7R an appealing target for anti-inflammatory and anti-cancer therapy. However, an in-depth knowledge of its structure and of the associated signal transduction mechanisms is needed for an effective therapeutic development.
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In the citing paper
“P2X7, which is widely expressed by immune cells, is the most studied purinergic receptors involved in neurodegeneration.374,375”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [374]
Experimental — accuracy not yet measuredIn the citing paper
“Hyperactivation of P2X7 receptors is closely related to inflammatory processes since they are stimulated by ATP released from distressed cells and induce inflammasome activation [16–18].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [16]
In the citing paper
“In these circumstances, ATP may act as DAMP, which activates the nuclear transcription factor NF-κB resulting in expression upregulation of pro-IL-1β and pro-IL-18 and the NLRP3 protein [16, 71].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [16]
In the citing paper
“Consequently, there is an activation of caspase-1 and maturation of IL-1β and IL-18, resulting in pro-inflammatory cytokine release [16, 20, 52, 71, 73].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [16]
In the citing paper
“The P2X7 receptor is a major activator of the NLRP3 inflammasome in several cell types [16], including macrophages and microglial cells [72, 74–76].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [16]
In the citing paper
“In fact, the role of P2X7 receptor as a modulator of inflammatory response is well-established [16, 70].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [16]
In the citing paper
“The massive ATP release following lung mononuclear phagocytes invasion by SARS-CoV-2 can activate P2X7 receptors of antigen-presenting cells and macrophages, increasing cytokine, chemokine and ATP secretion [16].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [16]
In the citing paper
“As discussed by Di Virgilio et al. [106], many processes associated with lung impairment, as seen in COVID-19 patients, are mediated by P2X7 receptors [16].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [16]
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Paxillin mediates ATP-induced activation of P2X7 receptor and NLRP3 inflammasome
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“However, P2X7, the purinergic receptor with the highest expression in msEGCs and the third highest in hEGC (Li ~ n (cid:2) an-Rico et al , 2016) that is also expressed on virtually all immune cell types (Di Virgilio et al , 2017), is not involved in the ATP-triggered reactive EGC phenotype.”
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“P2X7 positively regulates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death (12).”
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Self-citationPTEN expression by an oncolytic herpesvirus directs T-cell mediated tumor clearance
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“ATP, one of the major cancer metabolites and constituents of the TME (11, 12), serves as a key DAMP that activates NLRP3 inflammasome via the purinergic P2X7 receptors (13, 14).”
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“The P2X7R has a central role in inflammation as it is one of the most potent stimulator of the NLRP3 inflammasome, and therefore of caspase-1 activation and IL-1β and IL-18 release (Di Virgilio et al., 2017) (Figure 1).”
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“Previous studies have shown that P2X7R mediates NLRP3 inflammasome activation, leading to the release of cytokines and chemokines [111].”
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“The low level of K+ can directly result in the activation of the NLRP3 inflammasome [32,33].”
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“Activation of P2X7 pathways in DMD result in muscle cell damage and death along with increase inflammation.(82,83) One study was completed in male mdx mice to determine the outcome of suppressing P2X7 through a known allosteric inhibitor, zidovudine.”
BackgroundThe role and pharmacological properties of the P2X7 receptor in neuropathic pain
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“P2X7 receptor (P2X7R), a member of the P2X receptor family, is an ATP-gated, non-selective, ionotropic channel (Di Virgilio et al., 2017).”
BackgroundNLRP3 Inflammasome in Diabetic Cardiomyopathy and Exercise Intervention
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“Pyroptosis is a newly discovered form of programmed necrosis, and is characterized by cellular lysis and release of proinflammatory cytokines including IL-1β and IL-18 [14].”
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“Moreover, succinate could also activate autocrine/ paracrine signaling mediated by purinergic receptors, such as P2X4 and P2X7 ( 23 ).”
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Metadata
- Authors
- Di Virgilio, F., Dal Ben, D., Sarti, A. C., Giuliani, A. L., & Falzoni, S.
- Affiliations
- University of Ferrara (IT)
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 47
- Issue
- 1
- Pages
- 15-31
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2737555531
- Cited by
- 1,267
- References
- 199
- Citations by year
- 2026: 167 · 2025: 138 · 2024: 164 · 2023: 155 · 2022: 160 · 2021: 161 · 2020: 132 · 2019: 102 · 2018: 78 · 2017: 9
- FWCI
- 9.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Unicam Scientific Publications (University of Camerino) (submittedVersion, other-oa)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by)
- Funders
- Italian Association for Cancer Research (IG 13025, IG 18581)
- Telethon of Italy (GGP06070)
- ERA-NET Neuron Joint Transnational Project “Nanostroke,” the Ministry of Health of Italy (RF-2011-02348435)
- Italian Ministry of Education, University and Research (RBAP11FXBC_001)
- University of Ferrara
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Keywords
- P2X7 receptor, extracellular ATP, purinergic receptors, NLRP3 inflammasome, inflammation, innate immunity, adaptive immunity, cytokine and chemokine secretion, single nucleotide polymorphisms, cancer, anti-inflammatory therapy, cancer therapy, signal transduction, receptor structure
- MeSH terms
- Animals, Cell Differentiation, Humans, Infections, Inflammation, Macrophages, T-Lymphocytes, Receptors, Purinergic P2X7, Inflammasomes, Purinergic P2X Receptor Agonists
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