Expression and activity of AIM2-inflammasome in rheumatoid arthritis patients

Immunobiology. 2020 Mar;225(2):151880. doi: 10.1016/j.imbio.2019.11.015. Epub 2019 Dec 2.

Abstract

Introduction: AIM2 inflammasome activation leads to the release of IL-β, which plays an important role in rheumatoid arthritis pathogenesis. In this work, we evaluated AIM2 expression and activity in RA patients and healthy controls.

Methods: AIM2 and RANKL expression were evaluated by flow cytometry. Inflammasome activity was determined in monocyte cultures stimulated with synthetic DNA by measuring IL-1β levels in supernatants using an ELISA assay. The caspase-1 expression in monocytes was measured by western blot, the POP3 expression was analysed by qPCR, and serum levels of IFN-γ were evaluated using ELISA assay.

Results: We observed a diminution of CD14+AIM2+ cells in RA patients, associated with disease activity and evolution. Likewise, the levels of IL-1β were increased in monocyte cultures un-stimulated and stimulated with LPS from RA patients with DAS28 ≥ 4. The Caspase-1 activity and RANKL + monocytes in RA patients were slightly increased. Finally, augmented POP3 expression and diminished IFN-γ serum levels were detected in RA patients.

Conclusion: Our results showed that the monocytes from RA patients were prone to release IL-1β in the absence of the AIM2 inflammasome signal. The down-regulation of AIM2 to a systemic level in RA patients might be a consequence of augmented POP3 expression and might imply the survival of pro-inflammatory cells contributing to the inflammation process.

Keywords: AIM2; IL-1β; Inflammasome; Monocytes; Neutrophils; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / metabolism*
  • Caspase 1 / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Inflammasomes / metabolism*
  • Inflammation / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Monocytes / metabolism
  • mTOR Associated Protein, LST8 Homolog / metabolism

Substances

  • AIM2 protein, human
  • DNA-Binding Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharide Receptors
  • mTOR Associated Protein, LST8 Homolog
  • Interferon-gamma
  • Caspase 1