{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:15:35Z","timestamp":1791832535812,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Various stimuli, that is, mechanical stresses or inflammation, induce the release of adenosine triphosphate (ATP) by human periodontal ligament cells (HPDLCs). Extracellular adenosine triphosphate (eATP) affects HPDLCs\u2019 functions such as immunosuppressive action and inflammatory responses. Lipopolysaccharide (LPS) is the key factor involved in periodontal inflammation. However, the possible correlation and detailed mechanism of inflammation\u2010mediated eATP by LPS and inflammatory cascade formation in HPDLCs is unclarified. This study aims to examine the role of eATP on the HPDLCs\u2019 responses concerning inflammatory actions after LPS treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HPDLCs were stimulated with <jats:italic>Porphyromonas gingivalis<\/jats:italic> LPS and polyinosinic:polycytidylic acid (poly I:C). The amount of ATP release was measured at different time points using a bioluminescence assay. HPDLCs were treated with eATP. The expression of pro\u2010inflammatory and anti\u2010inflammatory genes was determined. Specific P<jats:sub>2<\/jats:sub>X purinoreceptor 7 (P<jats:sub>2<\/jats:sub>X<jats:sub>7<\/jats:sub>) inhibitors (brilliant blue G [BBG] and KN62), a specific P<jats:sub>2<\/jats:sub>Y purinoreceptor 1 (P<jats:sub>2<\/jats:sub>Y<jats:sub>1<\/jats:sub>) inhibitors (MRS2179), calcium chelator (EGTA), protein kinase C (PKC) inhibitors, nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells (NF\ud835\udf05B) activation inhibitors, and cyclic adenosine monophosphate (cAMP)\u2010dependent protein kinase A (PKA) inhibitors (H89 dihydrochloride) and activators (forskolin) were used to dissect the mechanism of eATP\u2010induced HPDLCs\u2019 inflammatory responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LPS and poly I:C induced ATP release. A low concentration of eATP (50\u00a0\u00b5M) increased pro\u2010inflammatory genes (<jats:italic>COX2, IL1B, IL6, IL8, IL12<\/jats:italic>, and <jats:italic>TNFA<\/jats:italic>), while a high concentration (500\u00a0\u00b5M) enhanced anti\u2010inflammatory genes (<jats:italic>IL4<\/jats:italic> and <jats:italic>IL10<\/jats:italic>). BBG, KN62, and NF\ud835\udf05B activation inhibitors impeded eATP\u2010induced pro\u2010inflammatory genes. MRS2179 and H89 markedly suppressed eATP\u2010induced anti\u2010inflammatory genes. Forskolin induced <jats:italic>IL4<\/jats:italic> and <jats:italic>IL10<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HPDLCs respond to LPS by releasing ATP. eATP has dose\u2010dependent dual functions on HPDLCs\u2019 inflammatory responses via different pathways. As regulation of inflammation is important in regeneration, eATP may help to limit inflammation and trigger periodontal regeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.23-0389","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T23:28:43Z","timestamp":1699313323000},"page":"281-295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Extracellular adenosine triphosphate regulates inflammatory responses of periodontal ligament cells"],"prefix":"10.1002","volume":"95","author":[{"given":"Maythwe","family":"Kyawsoewin","sequence":"first","affiliation":[{"name":"Dental Stem Cell Biology Research Unit and Department of Anatomy Faculty of Dentistry Chulalongkorn University  Bangkok Thailand"},{"name":"Center of Excellence for Regenerative Dentistry Chulalongkorn University  Bangkok 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