title: Neutrophil extracellular traps can serve as platforms for processing and activation of IL-1 family cytokines.
abstract: Activated neutrophils can undergo a mode of regulated cell death, called NETosis, that results in the extrusion of chromatin into the extracellular space, thereby acting as extracellular traps for microorganisms. Neutrophil-derived extracellular traps (NETs) are comprised of DNA decorated with histones, antimicrobial proteins and neutrophil granule proteases, such as elastase and cathepsin G (Cat G). NET-associated factors are thought to enhance the antimicrobial properties of these structures and localisation of antimicrobial molecules on NETs may serve to increase their local concentration. Because neutrophil-derived proteases have been implicated in the processing and activation of several members of the extended interleukin (IL)-1 family, we wondered whether neutrophil NETs could also serve as platforms for the activation of proinflammatory cytokines. Here, we show that neutrophil NETs potently processed and activated IL-1α as well as IL-36 subfamily cytokines through NET-associated Cat G and elastase. Thus, in addition to their role as antimicrobial traps, NETs can also act as local sites of cytokine processing and activation.
authors.affiliation: Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Clancy
authors.affiliation: Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
authors.forename: Conor M
authors.initials: CM
authors.lastname: Henry
authors.affiliation: Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Sullivan
authors.affiliation: Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
authors.forename: Seamus J
authors.initials: SJ
authors.lastname: Martin
mesh_terms: D056649:Cathepsin G / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000201:enzymology; D003850:Deoxyribonuclease I / Q000494:pharmacology; D065206:Extracellular Traps / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000097:blood; D007375:Interleukin-1 / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism*; D019272:Leukocyte Elastase / Q000378:metabolism*; D053146:Myeloblastin / Q000378:metabolism*; D018375:Neutrophil Activation / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: C508589:IL36G protein, human; D007375:Interleukin-1; D053582:Interleukin-1alpha; D011994:Recombinant Proteins; C572887:interleukin 36, human; D003850:Deoxyribonuclease I; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase; D053146:Myeloblastin; D013755:Tetradecanoylphorbol Acetate
keywords: IL-1 family; IL-1α, IL-36; NETs; cathepsin G; elastase; inflammation; neutrophil extracellular traps; protease