The synergistic pro-inflammatory effect of butyric and propionic acid on human periodontal ligament cells via activation of G-protein-coupled receptor 41.

PURPOSE: Periodontitis is a chronic disease that ultimately leads to tooth loss. This study aimed to investigate the inflammatory effects of short-chain fatty acids (SCFAs) on human periodontal ligament cells (hPDLCs).

METHODS

Immunofluorescence was employed to assess the expression of G protein-coupled receptors (GPRs) in hPDLCs. The Cell Counting Kit-8 and enzyme-linked immunosorbent assay kits were utilized to examine the regulatory effects of SCFAs on both the proliferation and secretion of pro-inflammatory factors in hPDLCs. Western blot analysis was performed to investigate the potential inflammatory responses in hPDLCs induced by SCFAs.

RESULTS

GPR41 was expressed on the surface of hPDLCs. The viability of hPDLCs was significantly reduced after exposure to both 7 mM butyric acid and 10 mM propionic acid. Additionally, a combination of 10 mM butyric acid and 10 mM propionic acid significantly increased the production of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in hPDLCs. Treatment with both 7 mM butyric acid and 10 mM propionic acid led to a significant increase in p65 phosphorylation in hPDLCs. There was no statistical difference in proliferation and pro-inflammatory effects after the addition of a GPR41 receptor inhibitor compared to the phosphate-buffered saline control.

CONCLUSIONS

Butyric acid and propionic acid exhibited a synergistic effect in inhibiting the proliferation of hPDLCs and enhancing their pro-inflammatory responses. This may be mediated through the activation of GPR41. Additionally, these acids could synergistically activate the nuclear factor-κB signaling pathway via GPR41 in hPDLCs.