Publication: Cell volume regulation modulates NLRP3 inflammasome activation
Authors
Compan, Vincent ; Baroja Mazo, Alberto ; López Castejón ∙, Gloria ; Gómez, Ana I. ; Martínez Cáceres, Carlos Manuel ; Angosto, Diego ; Montero, María T. ; Herranz, Antonio S. ; Bazán, Eulalia ; Reimers, Diana ; Mulero, Victoriano ; Pelegrín, Pablo
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Elsevier
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Description
© 2012 Elsevier Inc. This document is the Submitted, Accepted, Published, version of a Published Work that appeared in final form in Immunity. To access the final edited and published work see https://doi.org/10.1016/j.immuni.2012.06.013
Abstract
Cell volume regulation is a primitive response to alterations in environmental osmolarity. The NLRP3 inflammasome is a multiprotein complex that senses pathogen- and danger-associated signals. Here, we report that, from fish to mammals, the basic mechanisms of cell swelling and regulatory volume decrease (RVD) are sensed via the NLRP3 inflammasome. We found that a decrease in extracellular osmolarity induced a K+-dependent conformational change of the preassembled NLRP3-inactive inflammasome during cell swelling, followed by activation of the NLRP3 inflammasome and caspase-1, which was controlled by transient receptor potential channels during RVD. Both mechanisms were necessary for interleukin-1β processing. Increased extracellular osmolarity prevented caspase-1 activation by different known NLRP3 activators. Collectively, our data identify cell volume regulation as a basic conserved homeostatic mechanism associated with the formation of the NLRP3 inflammasome and reveal a mechanism for NLRP3 inflammasome activation.
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