TY - JOUR
T1 - Extracellular adenosine triphosphate induces IDO and IFNγ expression of human periodontal ligament cells through P2X7 receptor signaling
AU - Kyawsoewin, Maythwe
AU - Limraksasin, Phoonsuk
AU - Ngaokrajang, Utapin
AU - Pavasant, Prasit
AU - Osathanon, Thanaphum
N1 - Funding Information:
This work was supported by RTA 6180001 from the Thailand Science Research Innovation (TSRI). Maythwe Kyawsoewin was supported by Scholarship for ASEAN countries from Chulalongkorn University.
Publisher Copyright:
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2022/8
Y1 - 2022/8
N2 - 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 P2 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 P2 receptor was determined using calcium chelator (EGTA) and PKC inhibitor (PKCi). Chemical inhibitors (KN62 and BBG), small interfering RNA (siRNA), and P2X7 receptor agonist (BzATP) were used to confirm the involvement of P2X7 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 P2X7 inhibitors (KN62 and BBG) and siRNA targeting the P2X7 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 P2X7 receptor signaling. eATP may become a promising target for periodontal regeneration by modulating immune response and further triggering tissue healing.
AB - 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 P2 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 P2 receptor was determined using calcium chelator (EGTA) and PKC inhibitor (PKCi). Chemical inhibitors (KN62 and BBG), small interfering RNA (siRNA), and P2X7 receptor agonist (BzATP) were used to confirm the involvement of P2X7 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 P2X7 inhibitors (KN62 and BBG) and siRNA targeting the P2X7 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 P2X7 receptor signaling. eATP may become a promising target for periodontal regeneration by modulating immune response and further triggering tissue healing.
KW - IDO
KW - IFNγ
KW - PX receptor
KW - extracellular adenosine triphosphate
KW - periodontal ligament cells
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U2 - 10.1111/jre.12997
DO - 10.1111/jre.12997
M3 - Article
C2 - 35510301
AN - SCOPUS:85129235988
SN - 0022-3484
VL - 57
SP - 742
EP - 753
JO - Journal of Periodontal Research
JF - Journal of Periodontal Research
IS - 4
ER -