Periodontal ligament‐derived mesenchymal stem cells modulate neutrophil responses via paracrine mechanisms

Abstract Background Mesenchymal stem cells differentiate into distinct mesenchymal cell lineages and regulate the immune response. The aim of this study was to determine whether periodontal ligament‐derived mesenchymal stem cells (PDLSCs) have the ability to modulate neutrophil responses via paracrine mechanisms. Methods CD105‐enriched PDLSCs were seeded for 24 h and challenged with Porphyromonas gingivalis total protein extract ( Pg PE) (0 or 2 ug/mL) for 3 h. Cells were then washed and further cultured for 18 h and the supernatants were collected and stored. Next, neutrophil‐differentiated human promyelocytic leukemia HL‐60 cells (HL60D) were treated with PDLSCs supernatants and HL‐60D activation and functional responses were determined. Results Pg PE treatment induced higher secretion of inflammatory markers and chemokines by PDLSCs, including RANTES, eotaxin, interferon (IFN)‐γ‐ inducible protein 10 (IP‐10), monocyte chemoattractant protein‐1 (MCP‐1), IFN‐γ, interleukin (IL)‐6, IL‐8 and IL‐1ra ( P < 0.05). HL‐60D recruitment rate was increased by 4.7 ± 1.09‐fold when exposed to Pg PE‐treated PDLSCs supernatants. Pg PE‐treated PDLSCs supernatants promoted a 1.78 ± 1.04‐fold increase in the production of intracellular reactive oxygen species (ROS) by PMA‐stimulated HL‐60D, whereas Pg PE‐untreated PDLSCs supernatants led to a 16% reduction in intracellular ROS. In sharp contrast, neither Pg PE‐untreated nor Pg PE‐treated PDLSCs supernatants altered tumor necrosis factor (TNF)‐α and IL‐1β secretion by HL‐60D cells. Conclusion Together, these findings suggest an important role of PDLSCs in the recognition of P. gingivalis , paracrine recruitment and activation of antimicrobial mechanisms in innate immune cells, without interfering in cytokine responses.