A novel caspase-1 mediates inflammatory responses and pyroptosis in sea cucumber Apostichopus japonicus

Abstract

Caspase-1 is the most important inflammatory caspase and plays necessary roles in cell death. In the current study, a novel caspase-1 homolog was identified from sea cucumber Apostichopus japonicus; this homolog encoded a predicted protein containing a CASc domain with the pentapetide active site 173QACRG177. Ajcaspase-1 mRNA was ubiquitously expressed in all detected tissues, with higher levels found in respiratory trees and coelomocytes. Subcellular localization of Ajcaspase-1 mainly occurred in the nucleus. The transcript expression of Ajcaspase-1 was remarkably up-regulated in coelomocytes after Vibrio splendidus challenge in vivo and LPS stimulation in vitro. Recombinant Ajcaspase-1 (rAjcaspase-1) and the C-terminal of Ajcaspase-1 (rAjcaspase-1-C) revealed high levels of LPS binding activity and exhibited proteolytic activities toward the substrates Ac-YVAD-pNA and Ac-DEVD-pNA. The high activity of these enzymes in Ac-YVAD-pNA suggests that Ajcaspase-1 shares common caspase-1 activity. No obvious activities were detected for rAjcaspase-1-N. More importantly, rAjcaspase-1 significantly increased the expressions of HomoIL-1β and HomoGSDMD mRNA in HEK293 cells. Our results clearly indicate that Ajcaspase-1 may participate in the pyroptosis pathway by regulating inflammatory responses.