Enterococcus faecalis Activates Caspase-1 Leading to Increased Interleukin-1 Beta Secretion in Macrophages

Introduction: Recent studies of inflammasome activation have focused on the pathogenesis of diverse inflammatory and autoimmune diseases. Inflammasome activation results in caspase-1 activation, which is required for processing of prointerleukin (IL)-1 beta to its secreted form as well as a proinflammatory cell death (ie, pyroptosis). The purpose of this study was to analyze whether Enterococcus faecalis associated with endodontic infection induces inflammasome activation. Methods: THP-1 macrophages were treated with E. faecalis in the presence or absence of caspase-1 inhibitors. Caspase-1 activation, pro IL-1 beta expression, and IL-1 beta secretion were detected by immunoblotting, real-time reverse-transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Cell death was measured by lactate dehydrogenase release and propidium iodide staining. Adenosine triphosphate (ATP) release was measured by an ATP bioluminescence assay kit. Results: E. faecalis induced caspase-1 activation and pro IL-1 beta expression, which resulted in IL-1. beta secretion in macrophages. E. faecalis significantly induced ATP release, which is a mechanism of Nod-like receptor family protein 3 (NLRP3) inflammasome activation, whereas oxATP treatment inhibited E. faecalis induced caspase-1 activation. E. faecalis significantly increased lactate dehydrogenase release and propidium iodide uptake, which are characteristics of pyroptosis. Conclusions: Our results show that E. faecalis may contribute to the progression of pulpal inflammation by stimulating excessive secretion of IL-1 beta and cell death.