{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T21:43:58Z","timestamp":1787867038078,"version":"build-2784847793"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"publisher","award":["RTA6180001"],"award-info":[{"award-number":["RTA6180001"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mechanical stimuli induce the release of adenosine triphosphate into the extracellular environment by human periodontal ligament cells (hPDLCs). Extracellular adenosine triphosphate (eATP) plays the role in both inflammation and osteogenic differentiation. eATP involves in immunosuppressive action by increasing immunosuppressive molecules IDO and IFN\u03b3 expression on immune cells. However, the role of eATP on the immunomodulation of hPDLCs remains unclear. This study aimed to examine the effects of eATP on the IDO and IFN\u03b3 expression of hPDLCs and the participation of purinergic P<jats:sub>2<\/jats:sub> receptors in this phenomenon.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>hPDLCs were treated with eATP. The mRNA and protein expression of indoleamine\u2010pyrrole 2,3\u2010dioxygenase (IDO) and interferon\u2010gamma (IFN\u03b3) were determined. The role of the purinergic P<jats:sub>2<\/jats:sub> receptor was determined using calcium chelator (EGTA) and PKC inhibitor (PKCi).\u00a0Chemical inhibitors (KN62 and BBG), small interfering RNA (siRNA), and P<jats:sub>2<\/jats:sub>X<jats:sub>7<\/jats:sub> receptor agonist (BzATP) were used to confirm the involvement of P<jats:sub>2<\/jats:sub>X<jats:sub>7<\/jats:sub> receptors on IDO and IFN\u03b3 induction by hPDLCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>eATP significantly enhanced mRNA expression of IDO and IFN\u03b3. Moreover, eATP increased kynurenine which is the active metabolite of tryptophan breakdown catalyzed by the IDO enzyme and significantly induced IFN\u03b3 protein expression. EGTA and PKCi reduced eATP\u2010induced IDO and IFN\u03b3 expressions by hPDLCs, confirming the role of calcium signaling. Chemical P<jats:sub>2<\/jats:sub>X<jats:sub>7<\/jats:sub> inhibitors (KN62 and BBG) and siRNA targeting the P<jats:sub>2<\/jats:sub>X<jats:sub>7<\/jats:sub> receptor significantly inhibited the eATP\u2010induced IDO and IFN\u03b3 production. Correspondingly, BzATP markedly increased IDO and IFN\u03b3 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>eATP induced immunosuppressive function of hPDLCs by promoting IDO and IFN\u03b3 production via P<jats:sub>2<\/jats:sub>X<jats:sub>7<\/jats:sub> receptor signaling. eATP may become a promising target for periodontal regeneration by modulating immune response and further triggering tissue healing.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12997","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T06:35:36Z","timestamp":1651732536000},"page":"742-753","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Extracellular adenosine triphosphate induces IDO and IFN\u03b3 expression of human periodontal ligament cells through P<sub>2<\/sub>X<sub>7<\/sub> receptor signaling"],"prefix":"10.1111","volume":"57","author":[{"given":"Maythwe","family":"Kyawsoewin","sequence":"first","affiliation":[{"name":"Center of Excellence for Regenerative Dentistry Chulalongkorn University  Bangkok Thailand"},{"name":"Department of Oral Biological Science University of Dental Medicine  Yangon Myanmar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6189-8657","authenticated-orcid":false,"given":"Phoonsuk","family":"Limraksasin","sequence":"additional","affiliation":[{"name":"Center of Excellence for Regenerative Dentistry Chulalongkorn University  Bangkok Thailand"},{"name":"Department of Anatomy Faculty of Dentistry Chulalongkorn University  Bangkok Thailand"},{"name":"Division of Molecular and Regenerative Prosthodontics Tohoku University Graduate School of Dentistry  Sendai 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