Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Behm, Christian, Blufstein, Alice, Gahn, Johannes, Kubin, Barbara, Moritz, Andreas, Rausch-Fan, Xiaohui, Andrukhov, Oleh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765527/
https://www.ncbi.nlm.nih.gov/pubmed/33339125
http://dx.doi.org/10.3390/cells9122696
_version_ 1783628510992007168
author Behm, Christian
Blufstein, Alice
Gahn, Johannes
Kubin, Barbara
Moritz, Andreas
Rausch-Fan, Xiaohui
Andrukhov, Oleh
author_facet Behm, Christian
Blufstein, Alice
Gahn, Johannes
Kubin, Barbara
Moritz, Andreas
Rausch-Fan, Xiaohui
Andrukhov, Oleh
author_sort Behm, Christian
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7765527
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-77655272020-12-27 Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells Behm, Christian Blufstein, Alice Gahn, Johannes Kubin, Barbara Moritz, Andreas Rausch-Fan, Xiaohui Andrukhov, Oleh Cells Article 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. MDPI 2020-12-16 /pmc/articles/PMC7765527/ /pubmed/33339125 http://dx.doi.org/10.3390/cells9122696 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Behm, Christian
Blufstein, Alice
Gahn, Johannes
Kubin, Barbara
Moritz, Andreas
Rausch-Fan, Xiaohui
Andrukhov, Oleh
Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells
title Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells
title_full Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells
title_fullStr Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells
title_full_unstemmed Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells
title_short Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells
title_sort continuing effect of cytokines and toll-like receptor agonists on indoleamine-2,3-dioxygenase-1 in human periodontal ligament stem/stromal cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765527/
https://www.ncbi.nlm.nih.gov/pubmed/33339125
http://dx.doi.org/10.3390/cells9122696
work_keys_str_mv AT behmchristian continuingeffectofcytokinesandtolllikereceptoragonistsonindoleamine23dioxygenase1inhumanperiodontalligamentstemstromalcells
AT blufsteinalice continuingeffectofcytokinesandtolllikereceptoragonistsonindoleamine23dioxygenase1inhumanperiodontalligamentstemstromalcells
AT gahnjohannes continuingeffectofcytokinesandtolllikereceptoragonistsonindoleamine23dioxygenase1inhumanperiodontalligamentstemstromalcells
AT kubinbarbara continuingeffectofcytokinesandtolllikereceptoragonistsonindoleamine23dioxygenase1inhumanperiodontalligamentstemstromalcells
AT moritzandreas continuingeffectofcytokinesandtolllikereceptoragonistsonindoleamine23dioxygenase1inhumanperiodontalligamentstemstromalcells
AT rauschfanxiaohui continuingeffectofcytokinesandtolllikereceptoragonistsonindoleamine23dioxygenase1inhumanperiodontalligamentstemstromalcells
AT andrukhovoleh continuingeffectofcytokinesandtolllikereceptoragonistsonindoleamine23dioxygenase1inhumanperiodontalligamentstemstromalcells