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Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells

1
Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, Austria
2
Division of Orthodontics, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, Austria
3
Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Cells 2020, 9(12), 2696; https://doi.org/10.3390/cells9122696
Received: 21 October 2020 / Revised: 3 December 2020 / Accepted: 14 December 2020 / Published: 16 December 2020
(This article belongs to the Special Issue Oral Stem Cells in Tissue Engineering and Regenerative Medicine)
Transplanted mesenchymal stem/stromal cells (MSCs) are a promising and innovative approach in regenerative medicine. Their regenerative potential is partly based upon their immunomodulatory activities. One of the most investigated immunomediators in MSCs, such as in periodontal ligament-derived MSCs (hPDLSCs), is indoleamine-2,3-dioxygenase-1 (IDO-1) which is upregulated by inflammatory stimuli, like cytokines. However, there are no data concerning continuing IDO-1 expression in hPDLSCs after the removal of inflammatory stimuli, such as cytokines and toll-like receptor (TLR) agonist-2 and TLR-3. Hence, primary hPDLSCs were stimulated with interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, TLR-2 agonist Pam3CSK4 or TLR-3 agonist Poly I/C. IDO-1 gene and protein expression and its enzymatic activity were measured up to five days after removing any stimuli. IL-1β- and TNF-α-induced IDO-1 expression and enzymatic activity decreased in a time-dependent manner after cessation of stimulation. IFN-γ caused a long-lasting effect on IDO-1 up to five days after removing IFN-γ. Both, TLR-2 and TLR-3 agonists induced a significant increase in IDO-1 gene expression, but only TLR-3 agonist induced significantly higher IDO-1 protein expression and enzymatic activity in conditioned media (CM). IDO-1 activity of Poly I/C- and Pam3CSK4-treated hPDLSCs was higher at one day after removal of stimuli than immediately after stimulation and declined to basal levels after five days. Among all tested stimuli, only IFN-γ was able to induce long-lasting IDO-1 expression and activity in hPDLSCs. The high plasticity of IDO-1 expression and its enzymatic activity in hPDLSCs due to the variable cytokine and virulence factor milieu and the temporal-dependent responsiveness of hPDLSCs may cause a highly dynamic potential of hPDLSCs to modulate immune responses in periodontal tissues. View Full-Text
Keywords: human periodontal ligament stromal cell; immunomodulation; indoleamine-2,3-dioxygenase-1; cytokines; toll like receptor agonist human periodontal ligament stromal cell; immunomodulation; indoleamine-2,3-dioxygenase-1; cytokines; toll like receptor agonist
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MDPI and ACS Style

Behm, C.; Blufstein, A.; Gahn, J.; Kubin, B.; Moritz, A.; Rausch-Fan, X.; Andrukhov, O. Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells. Cells 2020, 9, 2696. https://doi.org/10.3390/cells9122696

AMA Style

Behm C, Blufstein A, Gahn J, Kubin B, Moritz A, Rausch-Fan X, Andrukhov O. Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells. Cells. 2020; 9(12):2696. https://doi.org/10.3390/cells9122696

Chicago/Turabian Style

Behm, Christian; Blufstein, Alice; Gahn, Johannes; Kubin, Barbara; Moritz, Andreas; Rausch-Fan, Xiaohui; Andrukhov, Oleh. 2020. "Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells" Cells 9, no. 12: 2696. https://doi.org/10.3390/cells9122696

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