Inflammatory response of uric acid produced by Porphyromonas gingivalis gingipains

Mol Oral Microbiol. 2020 Oct;35(5):222-230. doi: 10.1111/omi.12309. Epub 2020 Sep 4.

Abstract

Uric acid is a potential metabolite that serves as a danger-associated molecular pattern (DAMP) and induces inflammatory responses in sterile environments. Porphyromonas gingivalis is a keystone periodontopathogen, and its gingipain proteases play a critical role in the pathogenesis of periodontitis. In this study, we demonstrate that P. gingivalis gingipains play a role in THP-1 macrophage uric acid production by increasing the expression and activity of xanthine oxidoreductase (XOR). Uric acid sodium salt induces caspase-1 activation, cell death, and the expression of proinflammatory cytokines, including IL-1α, IL-6, and IL-8, in the human keratinocyte HOK-16B cell line. Our results suggest that gingipain-induced uric acid can mediate inflammation in periodontal tissue cells.

Keywords: P. gingivalis gingipains; caspase-1; uric acid; xanthine oxidoreductase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cytokines / metabolism
  • Gingipain Cysteine Endopeptidases / metabolism*
  • Humans
  • Inflammation
  • Keratinocytes
  • Porphyromonas gingivalis / enzymology*
  • Porphyromonas gingivalis / pathogenicity
  • THP-1 Cells
  • Uric Acid / metabolism*
  • Xanthine Dehydrogenase / metabolism

Substances

  • Cytokines
  • Gingipain Cysteine Endopeptidases
  • Uric Acid
  • Xanthine Dehydrogenase