Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
Department of Biomedical Science, University of Veterinary Medicine, Vienna, Austria.
Sci Rep. 2017 Oct 9;7(1):12856. doi: 10.1038/s41598-017-12480-7.
Periodontal ligament stem cells similarly to the mesenchymal stem cells of other tissues possess immunomodulatory properties, which are regulated by different cytokines, particularly by interferon-γ (IFN-γ). In contrast, less information is provided about the effect of toll-like receptors ligand on immunomodulatory properties of these cells. In the present study we investigated the response of human periodontal ligament stem cells (hPDLSCs) in response to simultaneous stimulation with IFN-γ and toll-like receptor (TLR) agonists. The resulting expression of indoleamine-2,3-dioxygenase-1 (IDO-1), interleukin (IL)-6, IL-8 and monocyte chemotactic protein 1 (MCP-1) was investigated. The expression of IDO-1 was upregulated by IFN-γ in both gene and protein levels. TLR2 agonists Pam3CSK4 induced gene expression of IDO-1, but had no effect on protein expression. IFN-γ induced IDO-1 protein expression was further enhanced by Pam3CSK4. TLR-4 agonist E. coli LPS has no significant effect on neither basal nor IFN-γ induced IDO-1 protein expression. The production of IL-6, IL-8, and MCP-1 was induced by TLR agonists. Neither basal nor TLR agonists induced production of these proteins was affected by IFN-γ. Our data shows potential interaction between IFN-γ and TLR2 responses in hPDLSCs, which might be involved in regulation of immune response in inflammatory diseases, and particularly periodontitis.
牙周膜干细胞与其他组织的间充质干细胞相似，具有免疫调节特性，这些特性受不同细胞因子的调节，尤其是干扰素-γ（IFN-γ）。相比之下，关于这些细胞的 Toll 样受体配体对免疫调节特性的影响的信息较少。在本研究中，我们研究了人牙周膜干细胞（hPDLSCs）在同时接受 IFN-γ和 Toll 样受体（TLR）激动剂刺激时的反应。研究了吲哚胺 2,3-双加氧酶-1（IDO-1）、白细胞介素（IL）-6、IL-8 和单核细胞趋化蛋白 1（MCP-1）的表达。研究了 IDO-1 的表达。IFN-γ在基因和蛋白水平上均上调 IDO-1 的表达。TLR2 激动剂 Pam3CSK4 诱导 IDO-1 的基因表达，但对蛋白表达没有影响。IFN-γ 诱导的 IDO-1 蛋白表达进一步增强了 Pam3CSK4 的作用。TLR-4 激动剂大肠杆菌 LPS 对基础和 IFN-γ诱导的 IDO-1 蛋白表达均无显著影响。TLR 激动剂诱导产生了 IL-6、IL-8 和 MCP-1。IFN-γ 既不影响基础表达，也不影响 TLR 激动剂诱导的这些蛋白质的产生。我们的数据显示 hPDLSCs 中 IFN-γ 和 TLR2 反应之间存在潜在的相互作用，这可能参与了炎症性疾病，特别是牙周炎中免疫反应的调节。
