Cell Volume Regulation Modulates NLRP3 Inflammasome Activation

Vincent Compan, Alberto Baroja-Mazo, Gloria López-Castejón, Ana I. Gomez, Carlos M. Martínez, Diego Angosto, María T. Montero, Antonio S. Herranz, Eulalia Bazán, Diana Reimers, Victoriano Mulero, Pablo Pelegrín

    Research output: Contribution to journalArticlepeer-review

    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. © 2012 Elsevier Inc.
    Original languageEnglish
    Pages (from-to)487-500
    Number of pages13
    JournalImmunity
    Volume37
    Issue number3
    DOIs
    Publication statusPublished - 21 Sept 2012

    Fingerprint

    Dive into the research topics of 'Cell Volume Regulation Modulates NLRP3 Inflammasome Activation'. Together they form a unique fingerprint.

    Cite this