AIM2 Inflammasome Is Critical for dsDNA-Induced IL-1β Secretion in Human Dental Pulp Cells

Inflammation. 2018 Mar;41(2):409-417. doi: 10.1007/s10753-017-0697-z.

Abstract

The AIM2 inflammasome pathway has been determined to play an important role in cellular immune defense against bacterial and viral infections; however, its function and regulatory mechanism in human dental pulp cells (HDPCs) during pulpitis remains poorly understood. In this study, we explored whether the AIM2 inflammasome pathway was activated in HDPCs in response to dsDNA and defined its role in regulating IL-1β secretion. We demonstrated that stimulation with IFN-γ and cytoplasmic DNA significantly activated the AIM2 inflammasome and increased IL-1β secretion in HDPCs. Moreover, AIM2 overexpression significantly up-regulated both cleaved Caspase-1 expression and IL-1β release in HDPCs, while suppression of ASC and Caspase-1 resulted in down-regulation of cleaved Caspase-1 and IL-1β secretion. These results suggest that Caspase-1-dependent IL-1β processing and secretion require the AIM2 inflammasome pathway in HDPCs and that the AIM2 inflammasome pathway is critical for regulation of the dental pulp immune response.

Keywords: IL-1β; absent in melanoma 2 (AIM2); cytoplasmic DNA; human dental pulp; inflammasome pathway.

MeSH terms

  • Caspase 1
  • Cells, Cultured
  • DNA / physiology*
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Dental Pulp / cytology
  • Dental Pulp / immunology
  • Dental Pulp / metabolism*
  • Humans
  • Inflammasomes / metabolism*
  • Inflammasomes / physiology
  • Interleukin-1beta / metabolism*
  • Pulpitis

Substances

  • AIM2 protein, human
  • DNA-Binding Proteins
  • Inflammasomes
  • Interleukin-1beta
  • DNA
  • Caspase 1