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

[1] Phospholipases C and A2 control lysosome-mediated IL-1β secretion:: Implications for inflammatory processes [J].

Andrei, C ;

Margiocco, P ;

Poggi, A ;

Lotti, LV ;

Torrisi, MR ;

Rubartelli, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (26) :9745-9750

[2] Synthesis and biological activity of N-arylpiperazine-modified analogues of KN-62, a potent antagonist of the purinergic P2X7 receptor [J].

Baraldi, PG ;

Nuñez, MD ;

Morelli, A ;

Falzoni, S ;

Di Virgilio, F ;

Romagnoli, R .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (08) :1318-1329

[3]

BARALDI PG, 2006, Patent No. 7094895

[4] Hit-to-lead studies:: The discovery of potent adamantane amide P2X7 receptor antagonists [J].

Baxter, A ;

Bent, J ;

Bowers, K ;

Braddock, M ;

Brough, S ;

Fagura, M ;

Lawson, M ;

McInally, T ;

Mortimore, M ;

Robertson, M ;

Weaver, R ;

Webborn, P .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (22) :4047-4050

[5]

BAXTER A, 2004, Patent No. 6242470

[6]

BEYER EC, 1991, J BIOL CHEM, V266, P7971

[7] Modulation of inflammation by extracellular nucleotides [J].

Boeynaems, Jean-Marie ;

Communi, Didier .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 (05) :943-944

[8] Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation [J].

Bours, M. J. L. ;

Swennen, E. L. R. ;

Di Virgilio, F. ;

Cronstein, B. N. ;

Dagnelie, P. C. .

PHARMACOLOGY & THERAPEUTICS, 2006, 112 (02) :358-404

[9] Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin [J].

Boyden, ED ;

Dietrich, WF .

NATURE GENETICS, 2006, 38 (02) :240-244

[10] Pannexins, a family of gap junction proteins expressed in brain [J].

Bruzzone, R ;

Hormuzdi, SG ;

Barbe, MT ;

Herb, A ;

Monyer, H .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (23) :13644-13649

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