Inflammatory response of uric acid produced by Porphyromonas gingivalis gingipains

• Published in: Molecular oral microbiology Vol. 35; no. 5; pp. 222 - 230
• Main Authors: Jun, Hye‐Kyung, An, Sun‐Jin, Kim, Hyun Young, Choi, Bong‐Kyu
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.10.2020
• Subjects: Acid production; Caspase; caspase‐1; Cell activation; Cell death; Cell Line; Cytokines; Cytokines - metabolism; Dentistry; Gingipain; Gingipain Cysteine Endopeptidases - metabolism; Humans; Inflammation; Inflammatory response; Keratinocytes; Macrophages; Metabolites; P. gingivalis gingipains; Pathogenesis; Periodontitis; Porphyromonas gingivalis; Porphyromonas gingivalis - enzymology; Porphyromonas gingivalis - pathogenicity; Sodium salts; THP-1 Cells; Uric acid; Uric Acid - metabolism; Xanthine Dehydrogenase - metabolism; Xanthine oxidoreductase; xanthine oxidoreductase; P. gingivalis gingipains; caspase-1; uric acid
• ISSN: 2041-1006; 2041-1014
• DOI: 10.1111/omi.12309

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. The blurb content for the graphical abstrct is P. gingivalis gingipains induce uric acid production in THP‐1 macrophages by increasing the expression and activity of xanthine oxidoreductase. Uric acid sodium salt induces caspase‐1 activation, cell death, and the expression of proinflammatory cytokines in the human keratinocyte HOK‐16B cells.