{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:02:46Z","timestamp":1774594966556,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670993"],"award-info":[{"award-number":["81670993"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81371157"],"award-info":[{"award-number":["81371157"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471991"],"award-info":[{"award-number":["81471991"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Chronic periodontitis, one of the most prevalent oral diseases, is associated with <jats:italic>Porphyromonas gingivalis<\/jats:italic> (<jats:italic>Pg<\/jats:italic>) lipopolysaccharide (LPS) infection and has profound effects on type 2 diabetes mellitus (t2DM). Metformin, a well\u2010known antidiabetic agent, has been reported to exert anti\u2010inflammatory effects on various cells. This study aims to investigate the role of metformin on LPS\u2010influenced inflammatory response in human gingival fibroblasts (HGFs).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Dose\u2010dependent additive effects of metformin on LPS\u2010influenced HGFs were detected. Cell\u2010counting assay was used to determine effects of metformin and LPS on viability of HGFs. Enzyme\u2010linked immunosorbent assay and quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) were applied to detect levels of interleukin (IL)\u20101\u03b2, IL\u20106, and tumor necrosis factor (TNF)\u2010\u03b1 in differently treated cells. Activating transcription factor\u20103 (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\u2010PCR and Western blot.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Results showed that 5 \u03bcg\/mL <jats:italic>Pg<\/jats:italic> LPS and 0.1, 0.5, and 1 mM metformin exhibited no toxicity to HGFs, and metformin inhibited LPS\u2010influenced IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1 production in a dose\u2010dependent manner. Metformin and LPS could synergistically facilitate ATF3 expression, and ATF3 knockdown abolished inhibitory effects of metformin on LPS\u2010influenced inflammatory cytokine production in HGFs.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The present study confirms that metformin suppresses LPS\u2010enhanced IL\u20106, IL\u20101\u03b2, and TNF\u2010\u03b1 production in HGFs via increasing ATF3 expression.<\/jats:p>","DOI":"10.1902\/jop.2017.170168","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T14:57:15Z","timestamp":1495810635000},"source":"Crossref","is-referenced-by-count":33,"title":["Metformin Inhibits <i>Porphyromonas<\/i><i>gingivalis<\/i> Lipopolysaccharide\u2010Influenced Inflammatory Response in Human Gingival Fibroblasts via Regulating Activating Transcription Factor\u20103 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