The P2X7 receptor: a key player in IL-1 processing and release.
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 P2X(7) receptor, as a key player in both processes. A deeper understanding of the mechanism by which the P2X(7) 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.
Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Italy. dfr@unife.it
Davide
D
Ferrari
Cinzia
C
Pizzirani
Elena
E
Adinolfi
Roberto M
RM
Lemoli
Antonio
A
Curti
Marco
M
Idzko
Elisabeth
E
Panther
Francesco
F
Di Virgilio
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006801:Humans; D007375:Interleukin-1 / Q000145:classification / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D008024:Ligands; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7
D007375:Interleukin-1; D020382:Interleukin-18; D008024:Ligands; C546468:P2RX7 protein, human; D017472:Receptors, Interleukin-1; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate