P2X7 receptor activation induces cell death and CD23 shedding in human RPMI 8226 multiple myeloma cells

Farrell, Andrew W.; Gadeock, Safina; Pupovac, Aleta; Wang, Bin; Jalilian, Iman; Ranson, Marie; Sluyter, Ronald

doi:10.1016/j.bbagen.2010.07.001

Cited by 40 publications

(61 citation statements)

References 56 publications

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“…In various tumour cell lines and tissues, notably melanoma cells (including A375), breast cancer or mouse glioma, (over)expression of P2X7 has been reported. In some cases, P2X7 activation by ATP causes a decrease in tumour cell number [30][31][32][33]. On the contrary, P2X7 activation may support cell proliferation, tumour growth or metastatic activity [34,35].…”

Section: Discussionmentioning

confidence: 99%

Natural compounds with P2X7 receptor-modulating properties

Fischer

Urban

Immig

et al. 2013

Purinergic Signalling

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The adenosine 5′-triphosphate (ATP)-gated P2X7 receptor is a membrane-bound, non-selective cation channel, expressed in a variety of cell types. The P2X7 senses high extracellular ATP concentrations and seems to be implicated in a wide range of cellular functions as well as pathophysiological processes, including immune responses and inflammation, release of gliotransmitters and cytokines, cancer cell growth or development of neurodegenerative diseases. In the present study, we identified natural compounds and analogues that can block or sensitize the ATP (1 mM)-induced Ca 2+ response using a HEK293 cell line stably expressing human P2X7 and fluorometric imaging plate reader technology. For instance, teniposide potently blocked the human P2X7 at sub-miromolar concentrations, but not human P2X4 or rat P2X2. A marked block of ATPinduced Ca 2+ entry and Yo-Pro-1 uptake was also observed in human A375 melanoma cells and mouse microglial cells, both expressing P2X7. On the other hand, agelasine (AGL) and garcinolic acid (GA) facilitated the P2X7 response to ATP in all three cell populations. GA also enhanced the YO-PRO-1 uptake, whereas AGL did not affect the ATP-stimulated intracellular accumulation of this dye. According to the pathophysiological role of P2X7 in various diseases, selective modulators may have potential for further development, e.g. as neuroprotective or antineoplastic drugs.

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Section: Discussionmentioning

confidence: 99%

Natural compounds with P2X7 receptor-modulating properties

Fischer

Urban

Immig

et al. 2013

Purinergic Signalling

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“…Human HaCaT keratinocytes and murine J774 macrophages were obtained and cultured as described [17,18]. Cell lines were checked for Mycoplasma spp.…”

Section: Cellsmentioning

confidence: 99%

The P2X7 receptor is not essential for development of imiquimod-induced psoriasis-like inflammation in mice

Geraghty

Mansfield

Fuller

et al. 2017

Purinergic Signalling

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Psoriasis is a chronic inflammatory skin disorder, characterised by epidermal hyperplasia (acanthosis) and leukocyte infiltration of the skin. Current therapies are inadequate, highlighting the need for new therapeutic targets. The P2X7 receptor is implicated in the pathogenesis of psoriasis. This study investigated the role of P2X7 in imiquimod (IMQ)-induced psoriasis-like inflammation. Topically applied IMQ caused twofold greater ear swelling in BALB/c mice compared to C57BL/6 mice, which encode a partial loss-offunction missense mutation in the P2RX7 gene. However, there was no difference in histological skin pathology (acanthosis and leukocyte infiltration) between the two strains. IMQ treatment up-regulated P2X7 expression in skin from both mouse strains. Additionally, IMQ induced ATP release from cultured human keratinocytes, a process independent of cell death. Injection of the P2X7 antagonist Brilliant Blue G (BBG) but not A-804598 partly reduced ear swelling compared to vehicle-injected control mice. Neither antagonist altered skin pathology. Moreover, no difference in ear swelling or skin pathology was observed between C57BL/6 and P2X7 knock-out (KO) mice. Flow cytometric analysis of IMQtreated skin from C57BL/6 and P2X7 KO mice demonstrated similar leukocyte infiltration, including neutrophils, macrophages and T cells. In conclusion, this study demonstrates that P2X7 is not essential for development of IMQ-induced psoriasis-like inflammation but does not exclude a role for this receptor in psoriasis development in humans or other mouse models of this disease.

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“…Consistent with this concept, human keratinocyte P2X7 co-localises with markers of apoptosis [16] , while P2X7 activation induces human keratinocyte death in vitro [17] and increases murine keratinocyte death in vivo [18] . P2X7 has been reported to be present on human HaCaT keratinocytes [19] and can mediate ATP-induced death of these cells [20] , although the presence of P2X7 in these cells has not been confirmed in all studies [21] . Nevertheless over-expression of protein kinase C alpha (PKCa) can result in increased expression of P2X7 in these cells [19] indicating that this kinase may be involved in the up-regulation of keratinocyte P2X7 in the upper layers of the epidermis.…”

Section: Keratinocytesmentioning

confidence: 97%

P2X7 receptor in skin biology and diseases

Geraghty¹,

Watson²,

Adhikary³

et al. 2016

WJD

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The P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer. AbstractThe P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer. Core tip: The P2X7 receptor is present on immune, stromal and epithelial cells. Activation of this receptor by its natural ligand, extracellular adenosine triphosphate, causes a variety of downstream effects including release of inflammatory mediators and growth factors, as well as cell death. P2X7 has various functions on skin cells, and studies of mouse models of disease and of human cells and tissues highlight emerging roles for this receptor in common skin disorders.

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P2X7 receptor activation induces cell death and CD23 shedding in human RPMI 8226 multiple myeloma cells

Cited by 40 publications

References 56 publications

Natural compounds with P2X7 receptor-modulating properties

Natural compounds with P2X7 receptor-modulating properties

The P2X7 receptor is not essential for development of imiquimod-induced psoriasis-like inflammation in mice

P2X7 receptor in skin biology and diseases

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