Quercetin protects oral mucosal keratinocytes against lipopolysaccharide-induced inflammatory toxicity by suppressing the AKT/AMPK/mTOR pathway

Immunopharmacol Immunotoxicol. 2021 Oct;43(5):519-526. doi: 10.1080/08923973.2021.1948565. Epub 2021 Jul 26.

Abstract

Background: Cytokines can induce a chronic inflammatory response in the periodontium, leading to periodontitis. Quercetin, a naturally occuring flavonoid, has been shown to inhibit periodontitis, but how it works is poorly understood. In this study, we assessed the impact of quercetin on lipopolysaccharide (LPS)-induced inflammatory damage in oral mucosal keratinocytes (hOMK107) and explored its underlying mechanism.

Methods: The viability and apoptosis of hOMK107 cells were measured after exposure to LPS, followed or not by quercetin. The production of IL-1β, IL-6, IL-8, TNF-ɑ, iNOS, and COX-2 was quantified by enzyme-linked immunosorbent assay (ELISA), while levels of Akt, AMPK, and mTOR and their phosphorylation were detected semi-quantitatively by western blotting.

Results: Quercetin significantly improved cell viability and apoptosis by reversing LPS-induced upregulation of Bax and downregulation of Bcl-2 in hOMK107 cells. Quercetin decreased the production of IL-1β, IL-6, IL-8, TNF-ɑ, iNOS, and COX-2, as well as signal transduction via the Akt/AMPK/mTOR pathway. Inhibitors of Akt, AMPK, and mTOR strengthened the anti-apoptotic effects of quercetin, while agonists of Akt, AMPK, or mTOR or Akt overexpression weakened the anti-apoptotic effects.

Conclusion: These results indicate that quercetin may have a potential protective effect against the chronic inflammation-related periodontitis via suppressing Akt/AMPK/mTOR pathway.

Keywords: Akt/AMPK/mTOR pathway; Quercetin; inflammation; oral mucosal keratinocyte cells; periodontitis.

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors*
  • AMP-Activated Protein Kinases / metabolism
  • Antioxidants / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cytoprotection / drug effects
  • Cytoprotection / physiology
  • Dose-Response Relationship, Drug
  • Humans
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Lipopolysaccharides / toxicity
  • Mouth Mucosa / cytology
  • Mouth Mucosa / drug effects*
  • Mouth Mucosa / metabolism
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quercetin / pharmacology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antioxidants
  • Inflammation Mediators
  • Lipopolysaccharides
  • Quercetin
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases