RT info:eu-repo/semantics/article
T1 Lipin-2 regulates NLRP3 inflammasome by affecting P2X7 receptor activation
A1 Lordén, Gema
A1 Sanjuán García, Itziar
A1 Pablo Herranz, Nagore de
A1 Meana González, Clara
A1 Álvarez Miguel, Ines
A1 Pérez García, María Teresa
A1 Pelegrín, Pablo
A1 Balsinde Rodríguez, Jesús
A1 Balboa García, María Ángeles
AB Mutations in human LPIN2 produce a disease known as Majeed syndrome, the clinical manifestations of which are ameliorated by strategies that block IL-1β or its receptor. However the role of lipin-2 during IL-1β production remains elusive. We show here that lipin-2 controls excessive IL-1β formation in primary human and mouse macrophages by several mechanisms, including activation of the inflammasome NLRP3. Lipin-2 regulates MAPK activation, which mediates synthesis of pro-IL-1β during inflammasome priming. Lipin-2 also inhibits the activation and sensitization of the purinergic receptor P2X7 and K+ efflux, apoptosis-associated speck-like protein with a CARD domain oligomerization, and caspase-1 processing, key events during inflammasome activation. Reduced levels of lipin-2 in macrophages lead to a decrease in cellular cholesterol levels. In fact, restoration of cholesterol concentrations in cells lacking lipin-2 decreases ion currents through the P2X7 receptor, and downstream events that drive IL-1β production. Furthermore, lipin-2-deficient mice exhibit increased sensitivity to high lipopolysaccharide doses. Collectively, our results unveil lipin-2 as a critical player in the negative regulation of NLRP3 inflammasome.
PB The Rockefeller University Press
SN 0022-1007
YR 2017
FD 2017
LK https://uvadoc.uva.es/handle/10324/79492
UL https://uvadoc.uva.es/handle/10324/79492
LA spa
NO Journal of Experimental Medicine, Feb 2017, vol. 214, n. 2, p. 511-528
NO Producción Científica
DS UVaDOC
RD 09-mar-2026