Proteolytic Processing of Interleukin-1 Family Cytokines: Variations on a Common Theme

• Published in: Immunity (Cambridge, Mass.) Vol. 42; no. 6; pp. 991 - 1004
• Main Authors: Afonina, Inna S., Müller, Christina, Martin, Seamus J., Beyaert, Rudi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.06.2015; Elsevier Limited
• Subjects: Angiogenesis; Animals; Arthritis; Caspase 1 - metabolism; Cytokines; Cytotoxicity; Grants; Humans; Immunity; Inflammation - immunology; Interleukin-1 - immunology; Interleukin-1 - metabolism; Ligands; Mast Cells - immunology; Neutrophils - immunology; Peptide Hydrolases - metabolism; Proteins; Proteolysis; Regulation
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2015.06.003

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. The members of the interleukin-1 family of cytokines are soluble mediators of inflammation. They are frequently synthesized as inactive “pro-forms” that require proteolytic processing for their bioactivity. In this review, Beyaert and colleagues survey the literature and provide a comprehensive synopsis of the role of proteases in activation of IL-1 family member cytokines.