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- Title
P2X7 receptor-stimulation causes fever via PGE2 and IL-1β release.
- Authors
Barberà-Cremades, Maria; Baroja.-Mazo, Alberto; Gomez, Ana I.; Machado, Francisco; Di Virgilio, Francesco; Pelegrín, Pablo
- Abstract
Prostaglandins (PGs) are important lipid mediators involved in the development of inflammatory associated pain and fever. PGE2 is a well-established endogenous pyrogen activated by proinflammatory cytokine interleukin (IL)-1β. P2X7 receptors (P2X7Rs) expressed by inflammatory cells are stimulated by the danger signal extracellular ATP to activate the inflammasome and release IL-1β. 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-1β 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 intraperitoneal LPS or IL-1β 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.
- Subjects
PROSTAGLANDINS; LIPIDS; PAIN; FEVER; INTERLEUKIN-1
- Publication
FASEB Journal, 2012, Vol 26, Issue 7, p2951
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.12-205765