Abstract
Human periodontal ligament stem cells (hPDLSCs) do not express membrane-bound CD14, and their responsiveness to bacterial lipopolysaccharide (LPS) is drastically enhanced by soluble CD14 (sCD14), which is due to the facilitation of the interaction between LPS and Toll-like receptor- (TLR-) 4. Several studies also show that sCD14 enhances the responsiveness of different immune cells to TLR-2, but such effect in hPDLSCs has not been studied so far. In the present study, we investigated for the first time the potential effect of sCD14 on the hPDLSC response to two different TLR-2 agonists, in vitro. Primary hPDLSCs were stimulated with synthetic lipopeptide Pam3CSK4 or lipoteichoic acid (LTA) in concentrations 1-1000 ng/ml in the presence/absence of sCD14 (250 ng/ml). Additionally, the effect of different sCD14 concentrations (2.5-250 ng/ml) on the TLR-2 response was determined in Pam3CSK4- or LTA-triggered hPDLSCs. The resulting expression of interleukin- (IL-) 6, chemokine C-X-C motif ligand 8 (CXCL8), and chemokine C-C motif ligand 2 (CCL2) was measured by qPCR and ELISA. The production of IL-6, CXCL8, and CCL2 was gradually increased by both TLR-2 agonists and was significantly enhanced by sCD14. The response of hPDLSCs to low and submaximal concentrations of TLR-2 agonists (1-100 ng/ml) was most effectively enhanced by sCD14. The effect of sCD14 on TLR-2 response in hPDLSCs was concentration-dependent and was already detectable at low sCD14 levels. Our data showed that exogenous sCD14 significantly enhanced the responsiveness of hPDLSCs to TLR-2 agonists and enabled the detection of their small amounts. This effect was already detectable at low sCD14 levels, which are comparable to those in saliva and gingival crevicular fluid. Changes in the local sCD14 level may be considered as a crucial factor influencing the susceptibility of hPDLSCs to different pathogens and thus may contribute to the progression of periodontitis.
Highlights
Mesenchymal stem cells (MSCs) are multipotent progenitor cells, exhibiting self-renewal potential and an ability to differentiate in vitro into multiple cell types [1]
Exogenous soluble CD14 (sCD14) significantly enhanced the expressions of IL-6, C-X-C motif ligand 8 (CXCL8), and C-C motif ligand 2 (CCL2) at submaximal Pam3CSK4 concentrations (1-100 ng/ml)
We focused on the expression of three proteins, IL-6, CXCL8, and CCL2, which are thought to play an essential role in periodontal tissue inflammation and are usually regarded as the factors which enhance the inflammatory response in periodontitis [41, 42]
Summary
Mesenchymal stem cells (MSCs) are multipotent progenitor cells, exhibiting self-renewal potential and an ability to differentiate in vitro into multiple cell types [1]. Human periodontal ligament stem cells (hPDLSCs) are a heterogenous population of fibroblast-like cells [6], which fulfils the minimal criteria for MSCs such as the expression of characteristic surface markers and the multilineage differentiation potential [6, 7]. Periodontitis is an inflammatory, multifactorial disease, leading to periodontal tissue destruction and may result in tooth loss in severe cases [10, 11]. It is associated with an impairment of host-microbial homeostasis, leading to an inappropriate, overwhelming immune response [12], and is affected by several risk factors including genetic predisposition [13] and smoking habits [14]. P. gingivalis and its virulence factors, like lipopolysaccharide (LPS) [18, 19] and various lipoproteins [20, 21], induce an inflammatory response in hPDLSCs and influence their immunomodulatory potential
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
