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The Journal of Immunology, 2006, 176: 3877-3883.
Copyright © 2006 by The American Association of Immunologists

BRIEF REVIEWS

The P2X7 Receptor: A Key Player in IL-1 Processing and Release1

Davide Ferrari2,*,{dagger}, Cinzia Pizzirani*,{dagger}, Elena Adinolfi*,{dagger}, Roberto M. Lemoli{ddagger}, Antonio Curti{ddagger}, Marco Idzko§, Elisabeth Panther§ and Francesco Di Virgilio*,{dagger}

* Department of Experimental and Diagnostic Medicine, Section of General Pathology, and {dagger} Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Ferrara, Italy; {ddagger} Institute of Haematology and Medical Oncology "L. & A. Seragnoli," University of Bologna, Bologna, Italy; and § Department of Pneumology, University of Freiburg, Freiburg, Germany.

Human IL-1 family proteins are key mediators of the host response to infections, injury, and immunologic challenges. The mechanism by which IL-1 activates proinflammatory responses in target cells, and the plasma membrane receptors involved, is fairly well known. This has led to the development of innovative drugs that block IL-1 downstream to its synthesis and secretion. On the contrary, the mechanism of IL-1 and other IL-1 family members (e.g., IL-18) maturation and release is incompletely understood. Accruing evidence points to a plasma membrane receptor for extracellular ATP, the P2X7 receptor, as a key player in both processes. A deeper understanding of the mechanism by which the P2X7 receptor triggers IL-1 maturation and exteriorization may suggest novel avenues for the treatment of inflammatory diseases and provide a deeper insight in the fundamental mechanism of protease activation and cellular export of proteins lacking a leader sequence.




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