Absent in melanoma 2 (AIM2) in rat dental pulp mediates the inflammatory response during pulpitis

J Endod. 2013 Nov;39(11):1390-4. doi: 10.1016/j.joen.2013.07.003. Epub 2013 Sep 4.

Abstract

Introduction: In recent years, the inflammasome has been determined to play an important role in inflammatory diseases. However, the role of the inflammasome in pulpitis remains unclear. Absent in melanoma 2 (AIM2) is a type of inflammasome that recognizes cytosolic double stranded DNA and forms a caspase-1-activating inflammasome with apoptosis-associated speck-like protein containing a caspase activating recruiting domain. In this study, we determined whether AIM2 was expressed in pulp cells and defined the role of AIM2 in the initiation of inflammation within the dental pulp.

Methods: In the in vivo study, the right maxillary molars from male adult Sprague-Dawley rats (250-350 g) were exposed to the pulp. In the in vitro study, the pulp cells isolated from the mandibular incisors of the Sprague-Dawley rats (2 weeks) were conventionally cultured. Immunofluorescence staining was used to determine the expression and distribution of AIM2 in the rat dental pulp tissues and cells in the presence or absence of inflammatory stimulation. Western blotting and real-time polymerase chain reaction were performed to determine whether there was a correlation between AIM2 expression levels and inflammation both in vivo and in vitro.

Results: In healthy dental pulp tissues and cells, AIM2 was only detected in the odontoblast layer. Stimulation significantly increased AIM2 expression in both the dental pulp tissues and cultured cells. The mRNA and protein levels of AIM2 were significantly up-regulated in response to inflammatory stimulation in a dose-dependent manner. Moreover, we also found that AIM2 expression correlated with interleukin-1 levels. These results reveal a direct relationship between the AIM2 inflammasome and pulpitis.

Conclusions: Our study demonstrates that AIM2 is expressed in dental pulp tissues and mediates the inflammatory response during pulpitis. Therapeutic interventions aimed at reducing AIM2 expression may be beneficial in the treatment of pulpitis.

Keywords: AIM2; IL-1β; caspase-1; inflammasome; rat dental pulp.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / physiology
  • Blotting, Western
  • CARD Signaling Adaptor Proteins
  • Caspase 1 / physiology
  • Cell Culture Techniques
  • Cells, Cultured
  • Cytoplasm / chemistry
  • Cytoplasm / ultrastructure
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / physiology*
  • Dental Pulp / cytology
  • Dental Pulp Exposure / pathology
  • Fibroblasts / chemistry
  • Fibroblasts / pathology
  • Fluorescent Antibody Technique
  • Inflammasomes / analysis
  • Inflammasomes / physiology*
  • Interferon-gamma / analysis
  • Interferon-gamma / physiology
  • Interleukin-1 / analysis
  • Lipopolysaccharides / pharmacology
  • Male
  • Odontoblasts / chemistry
  • Odontoblasts / pathology
  • Pulpitis / etiology*
  • Pulpitis / metabolism
  • Pulpitis / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation

Substances

  • AIM2 protein, rat
  • Apoptosis Regulatory Proteins
  • CARD Signaling Adaptor Proteins
  • DNA-Binding Proteins
  • Inflammasomes
  • Interleukin-1
  • Lipopolysaccharides
  • Pycard protein, rat
  • Interferon-gamma
  • Caspase 1