%0 Journal Article
%T IL©\1¦Á cleavage by inflammatory caspases of the noncanonical inflammasome controls the senescence©\associated secretory phenotype
%A Aled J. Parry
%A Jane C. Goodall
%A Kimberley A. Wiggins
%A Liam D. Cassidy
%A Masashi Narita
%A Melanie Humphry
%A Steve J. Webster
%J Archive of "Aging Cell".
%D 2019
%R 10.1111/acel.12946
%X Interleukin©\1 alpha (IL©\1¦Á) is a powerful cytokine that modulates immunity, and requires canonical cleavage by calpain for full activity. Mature IL©\1¦Á is produced after inflammasome activation and during cell senescence, but the protease cleaving IL©\1¦Á in these contexts is unknown. We show IL©\1¦Á is activated by caspase©\5 or caspase©\11 cleavage at a conserved site. Caspase©\5 drives cleaved IL©\1¦Á release after human macrophage inflammasome activation, while IL©\1¦Á secretion from murine macrophages only requires caspase©\11, with IL©\1¦Â release needing caspase©\11 and caspase©\1. Importantly, senescent human cells require caspase©\5 for the IL©\1¦Á©\dependent senescence©\associated secretory phenotype (SASP) in vitro, while senescent mouse hepatocytes need caspase©\11 for the SASP©\driven immune surveillance of senescent cells in vivo. Together, we identify IL©\1¦Á as a novel substrate of noncanonical inflammatory caspases and finally provide a mechanism for how IL©\1¦Á is activated during senescence. Thus, targeting caspase©\5 may reduce inflammation and limit the deleterious effects of accumulated senescent cells during disease and Aging
%K caspase
%K IL©\1
%K IL©\1 alpha
%K inflammasome
%K inflammation
%K senescence
%K senescence©\associated secretory phenotype
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516163/