Metformin Inhibits Porphyromonasgingivalis Lipopolysaccharide‐Influenced Inflammatory Response in Human Gingival Fibroblasts via Regulating Activating Transcription Factor‐3 Expression. Issue 10 (1st October 2017)

• Record Type: Journal Article
• Authors: Kang, Wenyan; Wang, Ting; Hu, Zhekai; Liu, Feng; Sun, Yundong; Ge, Shaohua
• Is Part Of: Journal of periodontology. Volume 88:Issue 10(2017)
• Page Start: e169
• Page End: e178
• Publication Date: 2017-10-01
• Subjects: Activating transcription factor 3; anti‐inflammatory agents -- cytokines -- diabetes mellitus -- fibroblasts -- periodontitis; Periodontics -- Periodicals; 617.632
• DOI: 10.1902/jop.2017.170168
• Languages: English
• ISSNs: 0022-3492

Abstract

Abstract : 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 well‐known antidiabetic agent, has been reported to exert anti‐inflammatory 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)‐1β, IL‐6, and tumor necrosis factor (TNF)‐α 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 μg/mL Pg LPS and 0.1, 0.5, and 1 mM metformin exhibited no toxicity to HGFs, and metformin inhibited LPS‐influenced IL‐1β, IL‐6, and TNF‐α 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‐1β, and TNF‐α production in HGFs via increasing ATF3 expression.