Metformin Inhibits Porphyromonas gingivalis Lipopolysaccharide-Influenced Inflammatory Response in Human Gingival Fibroblasts via Regulating Activating Transcription Factor-3 Expression

• Autores: Wenyan Kang, Jen-Ting Wang, Zhekai Hu, Feng Liu, Yundong Sun, Shaohua Ge
• Localización: Journal of periodontology, ISSN 0022-3492, Vol. 88, Nº. 10, 2017, págs. 169-178
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Background: Chronic periodontitis, one of the most prevalent oral diseases, is associated with Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) infection and has profound effects on type 2 diabetes mellitus (t2DM). Metformin, a wellknown antidiabetic agent, has been reported to exert antiinflammatory effects on various cells. This study aims to investigate the role of metformin on LPS-influenced inflammatory response in human gingival fibroblasts (HGFs).

    Methods: Dose-dependent additive effects of metformin on LPS-influenced HGFs were detected. Cell-counting assay was used to determine effects of metformin and LPS on viability of HGFs.

    Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to detect levels of interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a in differently treated cells. Activating transcription factor-3 (ATF3) small interfering (si)RNA transfection was used to determine the mechanism of metformin action, and the transfection efficiency was observed by fluorescence microscope. Effects of ATF3 knockdown were determined by qRT-PCR and Western blot.

    Results: Results showed that 5 mg/mL Pg LPS and 0.1, 0.5, and 1 mM metformin exhibited no toxicity to HGFs, and metformin inhibited LPS-influenced IL-1b, IL-6, and TNF-a production in a dose-dependent manner. Metformin and LPS could synergistically facilitate ATF3 expression, and ATF3 knockdown abolished inhibitory effects of metformin on LPS-influenced inflammatory cytokine production in HGFs.

    Conclusion: The present study confirms that metformin suppresses LPS-enhanced IL-6, IL-1b, and TNF-a production in HGFs via increasing ATF3 expression. J Periodontol 2017;88:

    e169-e178.