Liaisons dangereuses:: P2X7 and the inflammasome

被引：416

作者：

Di Virgilio, Francesco ^{[1
]}

机构：

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

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2007年 / 28卷 / 09期

关键词：

D O I：

10.1016/j.tips.2007.07.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Inflammation is initiated by specific pathogen constituents, in addition to intrinsic host molecules that are released by injured or dying cells. Among such host endogenous pro-inflammatory factors, nucleotides (mainly ATP) are attracting increasing interest for their potential as natural adjuvants. Extracellular ATP stimulates a family of receptors, named P2, one of which, P2X(7), is a potent mediator of interleukin (IL)-1 beta and IL-18 processing and release. The mechanism and physiological significance of this unusual pro-inflammatory activity have long remained elusive. Recent data unveiling the structure and function of a novel caspase-activating platform, the inflammasome, shed light on P2X(7) receptor coupling to IL-1 beta release, and suggest a fascinating scenario for the initiation and amplification of the innate immune response. Here, I outline the intriguing links between the P2X(7) receptor and the NALP3 inflammasome, review recent evidence showing that this receptor is a potent activator of this multimolecular platform and discuss implications for pathogen-immune cell interaction and for anti-inflammatory drug development.

引用

页码：465 / 472

页数：8

共 77 条

[51] Synthesis and SAR of novel 4,5-diarylimidazolines as potent P2X7 receptor antagonists [J].

Merriman, GH ;

Ma, L ;

Shum, P ;

McGarry, D ;

Volz, F ;

Sabol, JS ;

Gross, A ;

Zhao, ZC ;

Rampe, D ;

Wang, L ;

Wirtz-Brugger, F ;

Harris, BA ;

Macdonald, D .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (02) :435-438

[52] Intracellular pattern recognition receptors in the host response [J].

Meylan, Etienne ;

Tschopp, Juerg ;

Karin, Michael .

NATURE, 2006, 442 (7098) :39-44

[53] CD39 is the dominant Langerhans cell associated ecto-NTPDase:: Modulatory roles in inflammation and immune responsiveness [J].

Mizumoto, N ;

Kumamoto, T ;

Robson, SC ;

Sévigny, J ;

Matsue, H ;

Enjyoji, K ;

Takashima, A .

NATURE MEDICINE, 2002, 8 (04) :358-365

[54]

MURGIA M, 1993, J BIOL CHEM, V268, P8199

[55]

Nhieu GT, 2004, BIOL CELL, V96, P93, DOI 10.1016/j.biocel.2003.10.006

[56] Molecular physiology of P2X receptors [J].

North, RA .

PHYSIOLOGICAL REVIEWS, 2002, 82 (04) :1013-1067

[57] The inflammasome: First line of the immune response to cell stress [J].

Ogura, Yasunori ;

Sutterwala, Fayyaz S. ;

Flavell, Richard A. .

CELL, 2006, 126 (04) :659-662

[58] A ubiquitous family of putative gap junction molecules [J].

Panchin, Y ;

Kelmanson, I ;

Matz, M ;

Lukyanov, K ;

Usman, N ;

Lukyanov, S .

CURRENT BIOLOGY, 2000, 10 (13) :R473-R474

[59] Pannexin-1 couples to maitotoxin- and nigericin-induced interleukin-1β release through a dye uptake-independent pathway [J].

Pelegrin, Pablo ;

Surprenant, Annmarie .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (04) :2386-2394

[60] Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptor [J].

Pelegrin, Pablo ;

Surprenant, Annmarie .

EMBO JOURNAL, 2006, 25 (21) :5071-5082

← 1 2 3 4 5 6 7 8 →