Anti-inflammatory Effects of GW0742, a PPARδ Agonist, on Pulp Cells

Objectives: Identification and characterization of molecules able to dampen inflammatory events within the dental pulp, facilitating dentinal repair, offer a potential to increase the success in maintaining the tooth vitality. Due to its anti-inflammatory properties, the peroxisome proliferator-activated receptors delta (PPARδ) could be envisioned as a putative therapeutic target. Thus, the aim of this study was to assess the anti-inflammatory ability of GW0742, a PPARδ full agonist, on human dental pulp cells (hDPCs).
Methods: For this, hDPCs were treated with lipopolysaccharide (LPS)/Hydrogen peroxide (H₂O₂) or LSP/H₂O₂ plus GW0742 (10 nM, 100nM ou 1 μM), and real time SYBR^TM Green PCR was used to analyze cytokines (IL6; IL1β; MCP1) and metalloproteinases (MMP1,-2) mRNA expression. Also, a LPS or LPS plus GW0742 (1 μM) – conditioned hDPCs cultures were tested for their chemotactic effect on an immortalized murine macrophage cell line (RAW 264.7) in a transwell co-culture system.
Results: GW0742 repressed IL6, IL1β, MCP1 and MMP1 gene expression in LPS/H₂O₂ treated hDPCs (p < 0.05, with Kruskal-Wallis, followed by Dunn's Multiple Comparison Test). In addition, treatment with GW0742 significantly reduced the ability of LPS-stimulated pulp cells to recruit RAW 264.7 macrophages (p < 0.05, with one-way ANOVA, followed by Newman-Keuls Multiple Comparison Test).
Conclusions: GW0742 can modulate pulp inflammatory response, suggesting an anti-inflammatory effect of activated PPARδ receptor.