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The P2X7 Receptor-Interleukin-1 Liaison

Interleukin-1β (IL-1β) plays a central role in stimulation of innate immune system and inflammation and in several chronic inflammatory diseases. These include rare hereditary conditions, e.g., auto-inflammatory syndromes, as well as common pathologies, such as type II diabetes, gout and atheroscler...

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Autores principales: Giuliani, Anna Lisa, Sarti, Alba C., Falzoni, Simonetta, Di Virgilio, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353276/
https://www.ncbi.nlm.nih.gov/pubmed/28360855
http://dx.doi.org/10.3389/fphar.2017.00123
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author Giuliani, Anna Lisa
Sarti, Alba C.
Falzoni, Simonetta
Di Virgilio, Francesco
author_facet Giuliani, Anna Lisa
Sarti, Alba C.
Falzoni, Simonetta
Di Virgilio, Francesco
author_sort Giuliani, Anna Lisa
collection PubMed
description Interleukin-1β (IL-1β) plays a central role in stimulation of innate immune system and inflammation and in several chronic inflammatory diseases. These include rare hereditary conditions, e.g., auto-inflammatory syndromes, as well as common pathologies, such as type II diabetes, gout and atherosclerosis. A better understanding of IL-1β synthesis and release is particularly relevant for the design of novel anti-inflammatory drugs. One of the molecules mainly involved in IL-1β maturation is the P2X7 receptor (P2X7R), an ATP-gated ion channel that chiefly acts through the recruitment of the NLRP3 inflammasome-caspase-1 complex. In this review, we will summarize evidence supporting the key role of the P2X7R in IL-1β production, with special emphasis on the mechanism of release, a process that is still a matter of controversy. Four different models have been proposed: (i) exocytosis via secretory lysosomes, (ii) microvesicles shedding from plasma membrane, (iii) release of exosomes, and (iv) passive efflux across a leaky plasma membrane during pyroptotic cell death. All these models involve the P2X7R.
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spelling pubmed-53532762017-03-30 The P2X7 Receptor-Interleukin-1 Liaison Giuliani, Anna Lisa Sarti, Alba C. Falzoni, Simonetta Di Virgilio, Francesco Front Pharmacol Pharmacology Interleukin-1β (IL-1β) plays a central role in stimulation of innate immune system and inflammation and in several chronic inflammatory diseases. These include rare hereditary conditions, e.g., auto-inflammatory syndromes, as well as common pathologies, such as type II diabetes, gout and atherosclerosis. A better understanding of IL-1β synthesis and release is particularly relevant for the design of novel anti-inflammatory drugs. One of the molecules mainly involved in IL-1β maturation is the P2X7 receptor (P2X7R), an ATP-gated ion channel that chiefly acts through the recruitment of the NLRP3 inflammasome-caspase-1 complex. In this review, we will summarize evidence supporting the key role of the P2X7R in IL-1β production, with special emphasis on the mechanism of release, a process that is still a matter of controversy. Four different models have been proposed: (i) exocytosis via secretory lysosomes, (ii) microvesicles shedding from plasma membrane, (iii) release of exosomes, and (iv) passive efflux across a leaky plasma membrane during pyroptotic cell death. All these models involve the P2X7R. Frontiers Media S.A. 2017-03-16 /pmc/articles/PMC5353276/ /pubmed/28360855 http://dx.doi.org/10.3389/fphar.2017.00123 Text en Copyright © 2017 Giuliani, Sarti, Falzoni and Di Virgilio. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Giuliani, Anna Lisa
Sarti, Alba C.
Falzoni, Simonetta
Di Virgilio, Francesco
The P2X7 Receptor-Interleukin-1 Liaison
title The P2X7 Receptor-Interleukin-1 Liaison
title_full The P2X7 Receptor-Interleukin-1 Liaison
title_fullStr The P2X7 Receptor-Interleukin-1 Liaison
title_full_unstemmed The P2X7 Receptor-Interleukin-1 Liaison
title_short The P2X7 Receptor-Interleukin-1 Liaison
title_sort p2x7 receptor-interleukin-1 liaison
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353276/
https://www.ncbi.nlm.nih.gov/pubmed/28360855
http://dx.doi.org/10.3389/fphar.2017.00123
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