Background: 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 IFNγ 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 IFNγ expression of hPDLCs and the participation of purinergic P receptors in this phenomenon.
Methods: hPDLCs were treated with eATP. The mRNA and protein expression of indoleamine-pyrrole 2,3-dioxygenase (IDO) and interferon-gamma (IFNγ) were determined. The role of the purinergic P receptor was determined using calcium chelator (EGTA) and PKC inhibitor (PKCi). Chemical inhibitors (KN62 and BBG), small interfering RNA (siRNA), and P X receptor agonist (BzATP) were used to confirm the involvement of P X receptors on IDO and IFNγ induction by hPDLCs.
Results: eATP significantly enhanced mRNA expression of IDO and IFNγ. Moreover, eATP increased kynurenine which is the active metabolite of tryptophan breakdown catalyzed by the IDO enzyme and significantly induced IFNγ protein expression. EGTA and PKCi reduced eATP-induced IDO and IFNγ expressions by hPDLCs, confirming the role of calcium signaling. Chemical P X inhibitors (KN62 and BBG) and siRNA targeting the P X receptor significantly inhibited the eATP-induced IDO and IFNγ production. Correspondingly, BzATP markedly increased IDO and IFNγ expression.
Conclusion: eATP induced immunosuppressive function of hPDLCs by promoting IDO and IFNγ production via P X receptor signaling. eATP may become a promising target for periodontal regeneration by modulating immune response and further triggering tissue healing.
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