title: Enterococcus faecalis activates caspase-1 leading to increased interleukin-1 beta secretion in macrophages.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Ha-Hymn
authors.initials: HH
authors.lastname: Yang
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hye-Kyoung
authors.initials: HK
authors.lastname: Jun
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Young-Jung
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea; Dental Research Institute, Seoul National University, Seoul, Republic of Korea. Electronic address: bongchoi@snu.ac.kr.
authors.forename: Bong-Kyu
authors.initials: BK
authors.lastname: Choi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D002352:Carrier Proteins / Q000276:immunology; D020170:Caspase 1 / Q000276:immunology*; D061945:Caspase Inhibitors / Q000494:pharmacology; D018929:Cell Culture Techniques; D002460:Cell Line; D004396:Coloring Agents; D013293:Enterococcus faecalis / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation; D016908:Gram-Positive Bacterial Infections / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D007375:Interleukin-1 / Q000032:analysis; D053583:Interleukin-1beta / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009842:Oligopeptides / Q000494:pharmacology; D011419:Propidium; D011498:Protein Precursors / Q000032:analysis; D011671:Pulpitis / Q000276:immunology / Q000382:microbiology; D000069292:Pyroptosis / Q000276:immunology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D004396:Coloring Agents; D058847:Inflammasomes; D007375:Interleukin-1; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D009842:Oligopeptides; D011498:Protein Precursors; C460579:benzyloxycarbonyltyrosyl-valyl-alanyl-aspartic acid fluoromethyl ketone; C043830:interleukin 1 precursor; C096429:L 709049; D011419:Propidium; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D020170:Caspase 1
keywords: Caspase-1; Enterococcus faecalis; inflammasome; interleukin-1 beta processing; pyroptosis