High-Glucose Media Reduced the Viability and Induced Differential Pro-Inflammatory Cytokines in Human Periodontal Ligament Fibroblasts

Biomolecules. 2023 Apr 19;13(4):690. doi: 10.3390/biom13040690.

Abstract

Hyperglycemic condition in diabetic patients tends to exacerbate periodontitis severity. Thus, the influence of hyperglycemia on the biological and inflammatory response of periodontal ligament fibroblasts (PDLFs) needs to be elucidated. In this study, PDLFs were seeded in media containing glucose concentrations (5.5, 25, or 50 mM) and stimulated with 1 µg/mL of lipopolysaccharide (LPS). PDLFs' viability, cytotoxicity, and the migration ability were determined. The mRNA expression of Interleukin (IL)-6, IL-10, and IL-23 (p19/p40), and Toll-like receptor (TLR)-4 were analyzed; at 6 and 24 h, protein expression of IL-6 and IL-10 was also determined. PDLFs grown in 50 mM glucose medium showed lower viability. The 5.5 mM glucose led to the highest percentage of wound closure compared to 25 mM and 50 mM glucose with/without LPS. Additionally, 50 mM glucose with LPS exhibited the least migration ability among all groups. The expression of IL-6 was amplified significantly in LPS-stimulated cells in 50 mM glucose medium. IL-10 was constitutively expressed in different glucose concentrations, and LPS stimulation decreased it. IL-23 p40 was up-regulated after LPS stimulation in 50 mM glucose concentration. TLR-4 was highly expressed after LPS stimulation in all glucose concentrations. Hyperglycemic conditions limit PDLF proliferation and migration, and enhance the expression of certain pro-inflammatory cytokines to induce periodontitis.

Keywords: diabetes mellitus; glucose; hyperglycemia; inflammatory response; periodontal ligament fibroblast; periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Culture Media
  • Cytokines* / genetics
  • Cytokines* / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Glucose* / metabolism
  • Glucose* / pharmacology
  • Humans
  • Hyperglycemia*
  • Interleukin-10 / metabolism
  • Interleukin-23 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / metabolism
  • Lipopolysaccharides / pharmacology
  • Periodontal Ligament* / cytology
  • Periodontal Ligament* / drug effects

Substances

  • Cytokines
  • Glucose
  • Interleukin-10
  • Interleukin-23
  • Interleukin-6
  • Lipopolysaccharides
  • Culture Media

Grants and funding

This research was funded by the College of Dentistry Research Center and Deanship of Scientific Research at King Saud University, Saudi Arabia (Project No. E-20-4963).