P2X7 receptor-stimulation causes fever via PGE2 and IL-1β release

被引：126

作者：

Barbera-Cremades, Maria ^{[1
]}

Baroja-Mazo, Alberto ^{[1
]}

Gomez, Ana I. ^{[1
]}

Machado, Francisco ^{[2
]}

Di Virgilio, Francesco ^{[3
]}

Pelegrin, Pablo ^{[1
]}

机构：

[1] Univ Hosp Virgen, Inflammat & Expt Surg Unit, Arrixaca Fdn Formac Invest Sanit Reg Murcia FFIS, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Murcia 30120, Spain

[2] Univ Hosp Virgen, Dept Gynecol & Obstet, Arrixaca Fdn Formac Invest Sanit Reg Murcia FFIS, Murcia 30120, Spain

[3] Univ Ferrara, Sect Gen Pathol, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy

来源：

FASEB JOURNAL | 2012年 / 26卷 / 07期

关键词：

inflammation; pyrogen; macrophages; purinergic receptors; in vivo bioluminescence; ACTIVATED PROTEIN-KINASE; P2X(7) RECEPTOR; EXTRACELLULAR ATP; ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN E-2; MESSENGER-RNA; MOUSE MODEL; INFLAMMATION; CYCLOOXYGENASE-2; MACROPHAGES;

D O I：

10.1096/fj.12-205765

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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)-1 beta. P2X7 receptors (P2X7Rs) expressed by inflammatory cells are stimulated by the danger signal extracellular ATP to activate the inflammasome and release IL-1 beta. 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 beta 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-1 beta 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.-Barbera-Cremades, M., Baroja-Mazo, A., Gomez, A. I., Machado, F., Di Virgilio, F., Pelegrin, P. P2X7 receptor-stimulation causes fever via PGE2 and IL-1 beta release. FASEB J. 26, 2951-2962 (2012). www.fasebj.org

引用

页码：2951 / 2962

页数：12

共 61 条

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