Enterococcus faecalis activates caspase-1 leading to increased interleukin-1 beta secretion in macrophages.

Abstract

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.

• Authors: Ha-Hymn Yang, Hye-Kyoung Jun, Young-Jung Jung, Bong-Kyu Choi
• Journal: Journal of endodontics (J Endod) Vol. 40 Issue 10 Pg. 1587-92 (Oct 2014) ISSN: 1878-3554 [Electronic] United States
• PMID: 25127933 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Chemical References

• Amino Acid Chloromethyl Ketones
• Carrier Proteins
• Caspase Inhibitors
• Coloring Agents
• Inflammasomes
• Interleukin-1
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Oligopeptides
• Protein Precursors
• benzyloxycarbonyltyrosyl-valyl-alanyl-aspartic acid fluoromethyl ketone
• interleukin 1 precursor
• L 709049
• Propidium
• Adenosine Triphosphate
• L-Lactate Dehydrogenase
• Caspase 1

Topics

• Adenosine Triphosphate (metabolism)
• Amino Acid Chloromethyl Ketones (pharmacology)
• Carrier Proteins (immunology)
• Caspase 1 (immunology)
• Caspase Inhibitors (pharmacology)
• Cell Culture Techniques
• Cell Line
• Coloring Agents
• Enterococcus faecalis (enzymology, immunology)
• Enzyme Activation
• Gram-Positive Bacterial Infections (immunology)
• Humans
• Inflammasomes (immunology)
• Interleukin-1 (analysis)
• Interleukin-1beta (metabolism)
• L-Lactate Dehydrogenase (analysis)
• Macrophages (drug effects, immunology, microbiology)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Oligopeptides (pharmacology)
• Propidium
• Protein Precursors (analysis)
• Pulpitis (immunology, microbiology)
• Pyroptosis (immunology)