Saturated Fatty Acids Modulate Inflammatory Responses of Periodontal Ligament Fibroblasts

Objectives: Periodontal disease has been shown to be more prevalent and severe in patients with type 2 diabetes and obesity. A common feature in these patients is elevated serum saturated free fatty acids (SFFAs). Human periodontal ligament fibroblast (hPDLF) is a cell type in the periodontium and has been proposed to play important roles in innate immune response during periodontitis. However, potential roles of SFFAs in immune responses and oxidative stress in hPDLFs are currently unknown. This study aimed to determine the effects of SFFAs on cytokine production and glutathione redox in hPDLFs. Methods: hPDLFs were treated with SFFAs namely, palmitic acid, stearic acid, myristic acid or the unsaturated FFA, oleic acid, for 24 hours. The effects of SFFAs on cell viability were determined by MTS assay. Cytokine expression was quantified by qPCR. To identify the signaling pathways responsible for SFFAs-mediated cytokine expression, hPDLFs were treated with inhibitors of NF-κB or MAPK (Mitogen Activated Protein Kinase) prior to treatment with SFFAs. The effects of SFFAs on cellular glutathione redox were investigated by biochemical assay. Results: SFFAs did not significantly affect cell viability. All SFFAs induced significant up-regulation of IL-6 and IL-8 expressions. In contrast, unsaturated FFA did not induce pro-inflammatory effects. Treatment of cells with inhibitors of NF-κB (BAY11-7082) and p38 MAPK (SB203580) resulted in significant reductions in IL-6 and IL-8 expressions after treatment with SFFAs. SFFAs exposure significantly affected glutathione redox. Conclusions: We have found that SFFAs and not unsaturated FFA increase IL-6 and IL-8 productions in hPDLFs in a NF-κB and p38 MAPK dependent manner. SFFAs also elicited significant oxidative stress in hPDLFs. This study provides the first evidence on the possible roles of SFFAs as a potentially significant component in the modulation of inflammation during periodontal disease. (Supported by R221-000-054-101 from Faculty of Dentistry, NUS)