Liaisons dangereuses: P2X(7) and the inflammasome.
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)-1beta 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-1beta 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.
Di Virgilio
Francesco
F
Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Via Borsari, 46, Ferrara, Italy. fdv@unife.it
D000255:Adenosine Triphosphate / Q000276:immunology; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology; D020169:Caspases / Q000276:immunology; D017630:Connexins / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D034521:Nuclear Matrix-Associated Proteins / Q000276:immunology; D018048:Receptors, Purinergic P2 / Q000276:immunology*; D058486:Receptors, Purinergic P2X7
D002352:Carrier Proteins; D017630:Connexins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D034521:Nuclear Matrix-Associated Proteins; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D020169:Caspases