A Caspase-1 Biosensor to Monitor the Progression of Inflammation In Vivo. Journal Article


Authors: Talley, S; Kalinina, O; Winek, M; Paik, W; Cannon, AR; Alonzo, F; Choudhry, MA; Knight, KL; Campbell, EM
Article Title: A Caspase-1 Biosensor to Monitor the Progression of Inflammation In Vivo.
Abstract: Inflammasomes are multiprotein complexes that coordinate cellular inflammatory responses and mediate host defense. Following recognition of pathogens and danger signals, inflammasomes assemble and recruit and activate caspase-1, the cysteine protease that cleaves numerous downstream targets, including pro-IL-1ß and pro-IL-18 into their biologically active form. In this study, we sought to develop a biosensor that would allow us to monitor the initiation, progression, and resolution of inflammation in living animals. To this end, we inserted a known caspase-1 target sequence into a circularly permuted luciferase construct that becomes bioluminescent upon protease cleavage. This biosensor was activated in response to various inflammatory stimuli in human monocytic cell lines and murine bone marrow-derived macrophages. Next, we generated C57BL/6 transgenic mice constitutively expressing the caspase-1 biosensor. We were able to monitor the spatiotemporal dynamics of caspase-1 activation and onset of inflammation in individual animals in the context of a systemic bacterial infection, colitis, and acute graft-versus-host disease. These data established a model whereby the development and progression of inflammatory responses can be monitored in the context of these and other mouse models of disease.
Journal Title: Journal of immunology (Baltimore, Md. : 1950)
Publisher: Unknown  
Date Published: 2019