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.