The role of the purinergic P2X7 receptor in inflammation

Abstract

The inflammatory process, orchestrated against a variety of injurious stimuli, is composed of three inter-related phases; initiation, propagation and resolution. Understanding the interplay between these three phases and harnessing the beneficial properties of inflammation whilst preventing its damaging effects, will undoubtedly lead to the advent of much needed therapies, particularly in chronic disease states. The P2X7 receptor (P2X7R) is increasingly recognised as an important cell surface regulator of several key inflammatory molecules including IL-1β, IL-18, TNF-α and IL-6. Moreover, as P2X7R-dependent cytokine production is driven by activating the inflammasome, antagonists of this receptor are likely to have therapeutic potential as novel anti-inflammatory therapies. The function of the P2X7R in inflammation, immunity and its potential role in disease will be reviewed and discussed.

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

“…Of the seven P2X subtypes, by far the strongest body of evidence for involvement in mediating neuroinflammation exists for P2X7 (Lister et al, 2007). Gene-linking and epidemiological studies have implicated P2X7 in a host of CNS diseases (Hansen et al, 2008;Ursu et al, 2014).…”

“…P2X7 receptor activation of the inflammasome in response to high extracellular concentrations of ATP seems to rely primarily on K þ efflux through the cell membrane (Bernier, 2012;Lister et al, 2007). P2X7 receptor activation leads to an increase in permeability to K þ , either directly through the P2X7 receptor pore, or through the opening of pannexin-1 hemichannels (Panx1).…”

“…oedema, redness, increased temperature and pain in the affected tissue) with a fifth sign, loss of function, attributed to Galen. By the identification of underlying molecular and cellular mechanisms, inflammation now assumes a substantially wider meaning, as a complex biological response to harmful stimuli, composed of three phases: initiation, propagation and resolution (Lister et al, 2007). While the principle functions of inflammation are to limit tissue damage and promote tissue repair (Nathan, 2002), inappropriate inflammatory responses, particularly when chronic, can lead to toxicity and cell loss (Hauss-Wegrzyniak et al, 2002).…”

LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells

“…In addition, disruption of cellular membrane caused by the high plasma glucose and FFAs [18] can contribute to the accumulation of extracellular ATP [19]. Evidence has indicated that the P2X7 receptor was involved in the process of inflammatory response and release of inflammatory mediators [20,21]. Our previous studies also showed that the P2X7 receptor played a major role in the transmission of inflammatory signals and contributed to the pathological process of sympathetic injury [6,10,[22][23][24][25].…”

Human neutrophils do not express purinergic P2X7 receptors

“…In blood, the ATP released by healthy cells in response to stimuli such as shear stress and cell swelling, by damaged cells, by vascular injury or by stimulated platelets, [14,34] is able to stimulate several leukocyte functions such as DNA synthesis, blastogenesis, cell-mediated killing, apoptosis, pro-inflammatory activities, adhesion to endothelial cells, shedding of CD62L and expression of Mac1 [2,28,37,40]. These effects are mediated by purinergic receptors that belong to the metabotropic (P2Y) and/or ionotropic (P2X 1 -P2X 7 ) type [6,25,33].…”