title: Proteolytic Processing of Interleukin-1 Family Cytokines: Variations on a Common Theme.
abstract: Members of the extended interleukin-1 (IL-1) cytokine family, such as IL-1, IL-18, IL-33, and IL-36, play a pivotal role in the initiation and amplification of immune responses. However, deregulated production and/or activation of these cytokines can lead to the development of multiple inflammatory disorders. IL-1 family members share a broadly similar domain organization and receptor signaling pathways. Another striking similarity between IL-1 family members is the requirement for proteolytic processing in order to unlock their full biological potential. Although much emphasis has been put on the role of caspase-1, another emerging theme is the involvement of neutrophil- and mast cell-derived proteases in IL-1 family cytokine processing. Elucidating the regulation of IL-1 family members by proteolytic processing is of great interest for understanding inflammation and immunity. Here, we review the identity of the proteases involved in the proteolytic processing of IL-1 family cytokines and the therapeutic implications in inflammatory disease.
authors.affiliation: Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, VIB, Technologiepark 927, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
authors.forename: Inna S
authors.initials: IS
authors.lastname: Afonina
authors.affiliation: Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, VIB, Technologiepark 927, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium.
authors.forename: Christina
authors.initials: C
authors.lastname: Müller
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
authors.affiliation: Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, VIB, Technologiepark 927, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052 Ghent, Belgium. Electronic address: rudi.beyaert@irc.vib-ugent.be.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D006801:Humans; D007109:Immunity; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010447:Peptide Hydrolases / Q000378:metabolism; D059748:Proteolysis
chemical_list: D007375:Interleukin-1; D010447:Peptide Hydrolases; D020170:Caspase 1