title: NLRP3 inflammasome activity is negatively controlled by miR-223.
abstract: Inflammasomes are multiprotein signaling platforms that form upon sensing microbe- or damage-associated molecular patterns. Upon their formation, caspase-1 is activated, leading to the processing of certain proinflammatory cytokines and the initiation of a special type of cell death, known as pyroptosis. Among known inflammasomes, NLRP3 takes on special importance because it appears to be a general sensor of cell stress. Moreover, unlike other inflammasome sensors, NLRP3 inflammasome activity is under additional transcriptional regulation. In this study, we identify the myeloid-specific microRNA miR-223 as another critical regulator of NLRP3 inflammasome activity. miR-223 suppresses NLRP3 expression through a conserved binding site within the 3' untranslated region of NLRP3, translating to reduced NLRP3 inflammasome activity. Although miR-223 itself is not regulated by proinflammatory signals, its expression varies among different myeloid cell types. Therefore, given the tight transcriptional control of NLRP3 message itself, miR-223 functions as an important rheostat controlling NLRP3 inflammasome activity.
authors.affiliation: Unit for Clinical Biochemistry, Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital, University of Bonn, 53127 Bonn, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Bauernfeind
authors.forename: Anna
authors.initials: A
authors.lastname: Rieger
authors.forename: Frank A
authors.initials: FA
authors.lastname: Schildberg
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Schmid-Burgk
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*; D002461:Cell Line, Transformed; D015536:Down-Regulation / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*; D007739:L Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D035683:MicroRNAs; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C525067:MIR223, human; C453881:NLRP3 protein, human