title: Cell volume regulation modulates NLRP3 inflammasome activation.
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.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Compan
authors.forename: Alberto
authors.initials: A
authors.lastname: Baroja-Mazo
authors.forename: Gloria
authors.initials: G
authors.lastname: López-Castejón
authors.forename: Ana I
authors.initials: AI
authors.lastname: Gomez
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Martínez
authors.forename: Diego
authors.initials: D
authors.lastname: Angosto
authors.forename: María T
authors.initials: MT
authors.lastname: Montero
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Herranz
authors.forename: Eulalia
authors.initials: E
authors.lastname: Bazán
authors.forename: Diana
authors.initials: D
authors.lastname: Reimers
authors.forename: Victoriano
authors.initials: V
authors.lastname: Mulero
authors.forename: Pablo
authors.initials: P
authors.lastname: Pelegrín
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D048429:Cell Size; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009994:Osmolar Concentration; D034622:RNA Interference; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D006982:Hypertonic Solutions; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; D020170:Caspase 1