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Simplified diagram outlining the findings of the work. We show that ECs that undergo necrosis without prior stimulation have no IL-1α activity. Priming with IL-1 or TNFα before necrosis induces caspase-1 cleavage of IL-1R2 and disassociation from IL-1α. ECs that subsequently undergo necrosis release calpain-cleaved fully active IL-1α that induces cytokine release and adhesion molecule expression in adjacent cells, thus amplifying inflammation.
