Abstract
Human periodontal ligament stromal cells (hPDLSCs) and gingival mesenchymal stromal cells (hGMSCs) are resident mesenchymal stromal cells (MSCs) of the periodontal tissue. The lipopolysaccharide (LPS) from Porphyromonas gingivalis is structurally distinct from that of other Gram-negative bacteria, and earlier studies linked this structural difference to a distinct virulence activity and the ability to activate toll-like receptor 2 (TLR-2), besides TLR-4 as commonly occurring upon LPS challenge. Later studies, in contrast, argue that TLR-2 activation by P. gingivalis LPS is due to lipoprotein contamination. In the present study, we aimed to define the influence of structure versus purity of P. gingivalis LPS on the immune response of hPDLSCs and hGMSCs. Cells were stimulated with commercially available “standard” P. gingivalis LPS, “ultrapure” P. gingivalis LPS, or “ultrapure” Escherichia coli LPS, and the expression of interleukin- (IL-) 8, IL-6, monocyte chemoattractant protein- (MCP-) 1, TLR-2, and TLR-4 was evaluated. The contribution of TLR-4 to the LPS-induced response was assessed using the specific TLR-4 inhibitor TAK-242. “Standard” P. gingivalis LPS induced significantly higher IL-8, IL-6, and MCP-1 production compared to the “ultrapure” LPS preparations, with no significant difference detectable for “ultrapure” LPS from P. gingivalis and E. coli. By using TAK-242, the response of hPDLSCs and hGMSCs to “ultrapure” LPS preparations was effectively inhibited to the levels comparable to those of nonstimulated controls. In contrast, high levels of response to “standard” LPS were observed, even in the presence of TAK-242. Our data show that the response of MSCs from periodontal tissue to LPS depends more on the purity of the LPS preparation than on the LPS source. Even a small amount of contaminating lipoproteins can drastically enhance the hPDLSCs' and hGMSCs; responsiveness to P. gingivalis LPS, which might also contribute to the progression of periodontal disease.
Highlights
Human periodontal ligament stromal cells and human gingiva-derived mesenchymal stromal cells isolated from periodontal ligament [1] and the gingiva [2], respectively, fulfil the minimal criteria of mesenchymal stromal cells (MSCs) [3] and have characteristics comparable to bone marrow-derived MSCs [4]
They can migrate into inflamed or regenerating tissue upon sensing different chemoattractant stimuli [5, 7, 8]. human gingiva-derived mesenchymal stromal cells (hGMSCs) and Human periodontal ligament stromal cells (hPDLSCs) comprise diverse functions such as regulating periodontal tissue homeostasis and regeneration and inflammatory responses in periodontal disease progression, which pinpoints a potential use of these cells as therapeutic tool for oral and extraoral tissue regeneration [7,8,9,10,11,12]
We investigated the effect of different P. gingivalis LPS preparations on the expression of IL-6, IL-8, and monocyte chemoattractant protein 1 (MCP-1) in hPDLSCs and hGMSCs
Summary
Human periodontal ligament stromal cells (hPDLSCs) and human gingiva-derived mesenchymal stromal cells (hGMSCs) isolated from periodontal ligament [1] and the gingiva [2], respectively, fulfil the minimal criteria of mesenchymal stromal cells (MSCs) [3] and have characteristics comparable to bone marrow-derived MSCs [4] Both cell types influence immune and inflammatory responses, by acting either as immunosuppressors, mainly by producing immunomediators, or as immunostimulators, by secreting various proinflammatory mediators [5, 6]. Lipopolysaccharide (LPS), a crucial virulence factor of P. gingivalis [16], induces the production of several proinflammatory mediators like interleukin- (IL-) 1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein 1 (MCP-1) by hPDLSCs [17,18,19] and hGMSCs [20,21,22] Production of these mediators contributes to an excessive inflammatory response, leading to the destruction of the periodontal tissue and to alveolar bone resorption [23]
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