Release of interleukin-1α or interleukin-1β depends on mechanism of cell death.
The cytokine interleukin-1 (IL-1) has two main pro-inflammatory forms, IL-1α and IL-1β, which are central to host responses to infection and to damaging sterile inflammation. Processing of IL-1 precursor proteins to active cytokines commonly occurs through activation of proteases, notably caspases and calpains. These proteases are instrumental in cell death, and inflammation and cell death are closely associated, hence we sought to determine the impact of cell death pathways on IL-1 processing and release. We discovered that apoptotic regulation of caspase-8 specifically induced the processing and release of IL-1β. Conversely, necroptosis caused the processing and release of IL-1α, and this was independent of IL-1β processing and release. These data suggest that the mechanism through which an IL-1-expressing cell dies dictates the nature of the inflammatory mechanism that follows. These insights may allow modification of inflammation through the selective targeting of cell death mechanisms during disease.
From the Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Hazel
H
England
From the Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Holly R
HR
Summersgill
From the Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Michelle E
ME
Edye
From the Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Nancy J
NJ
Rothwell
From the Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, United Kingdom david.brough@manchester.ac.uk.
David
D
Brough
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002478:Cells, Cultured; D053582:Interleukin-1alpha / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis
D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D002154:Calpain; D053181:Caspase 8; D002118:Calcium
Apoptosis; Calpain; Caspase; Cell Death; Inflammation; Interleukin; Macrophage; Necrosis (Necrotic Death)