Publication: P2X7 receptor-stimulation causes fever via PGE2 and IL-1beta release
Authors
Barbera-Cremades, Maria ; Baroja-Mazo, Alberto ; Gomez, Ana I. ; Machado, Francisco ; Di Virgilio, Francesco ; Pelegrín Vivancos, Pablo
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Publisher
Wiley
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DOI
10.1096/fj.12-205765
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info:eu-repo/semantics/article
Description
©2012. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This document is the Submitted version of a Published Work that appeared in final form in FASEB Journal,. To access the final edited and published work see https://doi.org/10.1096/fj.12-205765
Abstract
Prostaglandins (PG) are important lipid mediators involved in the development of inflammatory associated pain and fever. PGE2 is a well-established endogenous pyrogen activated by pro-inflammatory cytokine interleukin (IL)-1 . P2X7 receptors (P2X7R) expressed by inflammatory cells are stimulated by the danger signal extracellular ATP to activate the inflammasome and release IL-1 . Here we show that P2X7R activation is required for the release of PGE2 and other autacoids independent of inflammasome activation, with an ATP EC50 for PGE2 and IL-1 release of 1.58 and 1.23 mM, respectively. Furthermore, lack of P2X7R or specific antagonism of P2X7R decreased the febrile response in mice triggered after intra peritoneal (i.p.) LPS or IL-1 inoculation. Accordingly, LPS inoculation caused intraperitoneal ATP accumulation. Therefore, P2X7R antagonists emerge as novel therapeutics for the treatment for acute inflammation, pain and fever, with wider anti-inflammatory activity than currently used cyclooxygenase inhibitors.
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Citation
FASEB Journal, volumen 26, nº 7, año 2012, páginas 2951-2962
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/