Caspase-1-responsive fluorescence biosensors for monitoring endogenous inflammasome activation

The activation of inflammasome leads to secretion of inflammatory factors and cell pyroptosis that are critical in the pathogenesis of various chronic and acute inflammatory diseases. Recruitment and activation of caspase-1 is a marker of inflammasome activation. However, there is still lack of real-time and efficient methods to detect the activation of inflammasome, especially in vivo. Herein, we developed two activatable caspase-1-responsive fluorescence biosensors, WEHD-HCy and YVAD-HCy, to specifically monitor the activation of inflammasome in vivo. Our in vitro study demonstrated that WEHD-HCy and YVAD-HCy can sensitively and specifically respond to caspase-1 activation. Moreover, these biosensors can efficiency and specifically activated in the common inflammatory disease model, including inflammatory bowel disease, Salmonella infection, and acute arthritis. In particular, WEHD-HCy is more advantageous than YVAD-HCy to specifically image of caspase-1 activity both in vitro and in vivo. These caspase-1-responsive fluorescence biosensors provide an efficient, rapid, and in situ tool for monitoring inflammasome activation, and have the potential to be suitable for clinical diagnosis of various inflammatory diseases associated with inflammasome activation. Schematic illustration of caspase-1-responsive biosensor WEHD-HCy response to inflammasome activation and its widely application in vitro and in vivo. [Display omitted] •Two caspase-1-responsive fluorescence biosensors to specifically monitor the activation of inflammasome were developed.•The peptide substrate WEHD is more optimal than YVAD for sensitive and specifical response to caspase-1 in vitro.•WEHD-HCy is more advantageous than YVAD-HCy to monitor caspase-1 activity in the common inflammatory disease model in vivo.