Teneligliptin inhibits lipopolysaccharide-induced cytotoxicity and inflammation in dental pulp cells

Int Immunopharmacol. 2019 Aug:73:57-63. doi: 10.1016/j.intimp.2019.04.059. Epub 2019 May 9.

Abstract

Diabetes mellitus is one of the most common health threatening disorders. Patients with chronic diabetes are at high risk of contracting oral diseases, including dental pulp damage. In this study, we reviewed how Teneligliptin, a commonly used anti-diabetic agent, protected dental pulp cells from lipopolysaccharide (LPS)-induced cytotoxicity and improved their viability. The dental pulp cells treated with Teneligliptin were resistant to LPS-induced reactive oxygen species (ROS) and its byproduct 4-hydroxynonenal (4-HNE) generation. The Teneligliptin recovered LPS-induced a reduction of cellular glutathione and produced cytokine including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Mechanistically, we found that Teneligliptin suppressed LPS- that caused an expression of the cell surface receptor toll like receptor 4 (TLR-4) and the activation of JNK kinase and activator protein 1 (AP1) as well as the nuclear factor-κB (NF-κB) signal pathways. Collectively, our study demonstrates that the molecular mechanism Teneligliptin is a protective anti-diabetic agent in dental pulp cells and it has the potential to treat diabetes-associated dental pulp diseases.

Keywords: Diabetes mellitus; Human dental pulp cell; Lipopolysaccharide (LPS); Nuclear factor-κB; Teneligliptin.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Dental Pulp / cytology*
  • Glutathione / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Lipopolysaccharides
  • Oxidative Stress / drug effects
  • Pyrazoles / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Thiazolidines / pharmacology*
  • Toll-Like Receptor 4 / metabolism

Substances

  • 3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine
  • Anti-Inflammatory Agents
  • Cytokines
  • Hypoglycemic Agents
  • Lipopolysaccharides
  • Pyrazoles
  • Reactive Oxygen Species
  • TLR4 protein, human
  • Thiazolidines
  • Toll-Like Receptor 4
  • Glutathione